Nkx3-1

Summary

Gene Symbol: Nkx3-1
Description: NK-3 transcription factor, locus 1 (Drosophila)
Alias: Bax, NKX3.1, NKX3A, Nkx-3.1, bagpipe, homeobox protein Nkx-3.1, Drosophila NK-3 transcription factor, locus 1, homeobox protein NK-3 homolog A
Species: mouse

Top Publications

  1. ncbi Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis
    David M Berman
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Biol 267:387-98. 2004
  2. ncbi Prostate-specific and androgen-dependent expression of a novel homeobox gene
    C J Bieberich
    Department of Virology, Jerome H Holland Laboratory, Rockville, Maryland 20855, USA
    J Biol Chem 271:31779-82. 1996
  3. ncbi Expression of an Nkx3.1-CRE gene using ROSA26 reporter mice
    M N Stanfel
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
    Genesis 44:550-5. 2006
  4. ncbi Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis
    Yongshun Lin
    Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A and M Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030 3303, USA
    Development 134:723-34. 2007
  5. pmc Mouse Fem1b interacts with the Nkx3.1 homeoprotein and is required for proper male secondary sexual development
    Xi Wang
    Center for Advanced Biotechnology and Medicine, Departments of Pediatrics, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
    Dev Dyn 237:2963-72. 2008
  6. ncbi The smooth muscle gamma-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor
    J A Carson
    Department of Cellular and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 275:39061-72. 2000
  7. pmc Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis
    H Song
    Department of Pathology and Immunology, School of Medicine, Washington University at St Louis, St Louis, MO 63110, USA
    Oncogene 28:3307-19. 2009
  8. ncbi Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation
    Nan Gao
    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
    Development 132:3431-43. 2005
  9. ncbi Loss-of-function of Nkx3.1 promotes increased oxidative damage in prostate carcinogenesis
    Xuesong Ouyang
    Center for Advanced Biotechnology and Medicine, The Cancer Institute of New Jersey, Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 5638, USA
    Cancer Res 65:6773-9. 2005
  10. pmc Distinct regulatory elements mediate the dynamic expression pattern of Nkx3.1
    Hui Chen
    Department of Biological Sciences, University of Maryland Baltimore County, 21250, USA
    Dev Dyn 234:961-73. 2005

Research Grants

Scientific Experts

  • S Nagel
  • DAVID MONTY BERMAN
  • Sarki A Abdulkadir
  • Cory Abate-Shen
  • M M Shen
  • Russell D Klein
  • Robert D Cardiff
  • Andrea Califano
  • Antonina Mitrofanova
  • Alvaro Aytes
  • Xuesong Ouyang
  • Hui Gao
  • Carolyn Waugh Kinkade
  • Celine Lefebvre
  • Yongshun Lin
  • Monica Logan
  • Charles J Bieberich
  • Philip D Anderson
  • Kimberly P Keil
  • Xiuping Yu
  • Martin K Thomsen
  • Robert J Matusik
  • Whitney Banach-Petrosky
  • Xi Wang
  • Laura N Mutton
  • Simon W Hayward
  • Brian W Simons
  • Nicolas Floc'h
  • Warren E Zimmer
  • Whitney A Banach-Petrosky
  • Yan Zhang
  • Chunhong Lin
  • M Tanaka
  • Fen Wang
  • Ya Ping Hu
  • Yongyou Zhang
  • Bin Guan
  • Sam Goldsmith
  • Aditya Dutta
  • Urmila Santanam
  • Xiang Li
  • Minjung J Kim
  • Chee Wai Chua
  • Ming Lei
  • Sarah K Bergren
  • Feng Jin
  • Michael Ittmann
  • Zhu A Wang
  • Aparna Gupta
  • Pankaj Sharma
  • Chad M Vezina
  • Orla M Casey
  • Takashi Kobayashi
  • Vatsal Mehta
  • Lisa L Abler
  • Pinak S Joshi
  • Ruth L Vinall
  • Jingqiang Wang
  • Christopher T Schmitz
  • Erin E Martinez
  • Nishita Desai
  • K L Wells
  • Mireia Castillo-Martin
  • Xinyu Wu
  • Angelo M De Marzo
  • Tsuyoshi Iwata
  • May Khalili
  • Chinatsu Kojima
  • H Song
  • Qiang Sun
  • Erin Muhlbradt
  • Amanda Swain
  • Ching Ching Leow
  • Christopher M Butler
  • Sandy M Price
  • E Ullman
  • VERONICA R PLACENCIO
  • Olga Klezovitch
  • Alexander D Borowsky
  • J A Carson
  • Edward P Gelmann
  • William G Nelson
  • Jim W Xuan
  • Wallace L McKeehan
  • Ming Jiang
  • William L Gerald
  • Yu Takahashi
  • Jeong Ho Ju
  • Steven O Simmons
  • Qunying Lei

Detail Information

Publications84

  1. ncbi Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis
    David M Berman
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Biol 267:387-98. 2004
    ..Taken together, our studies indicate that the initial organogenesis of the prostate proceeds independently of Shh, but that Shh or other Hh ligands may play a role in subsequent events that pattern the prostate...
  2. ncbi Prostate-specific and androgen-dependent expression of a novel homeobox gene
    C J Bieberich
    Department of Virology, Jerome H Holland Laboratory, Rockville, Maryland 20855, USA
    J Biol Chem 271:31779-82. 1996
    ..1 protein, which likely functions as a transcription factor, plays a prominent role both in the initiation of prostate development and in the maintenance of the differentiated state of prostatic epithelial cells...
  3. ncbi Expression of an Nkx3.1-CRE gene using ROSA26 reporter mice
    M N Stanfel
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
    Genesis 44:550-5. 2006
    ..1-CRE; R26R and Nkx3.2-CRE; R26R embryos was observed in overlapping regions of the sclerotome but no apparent change in Nkx3.1 expression was seen in the Nkx3.2 mutants by in situ hybridization...
  4. ncbi Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis
    Yongshun Lin
    Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A and M Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030 3303, USA
    Development 134:723-34. 2007
    ....
  5. pmc Mouse Fem1b interacts with the Nkx3.1 homeoprotein and is required for proper male secondary sexual development
    Xi Wang
    Center for Advanced Biotechnology and Medicine, Departments of Pediatrics, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
    Dev Dyn 237:2963-72. 2008
    ..1 mutants. We propose that Fem1b may have a conserved role in the generation of sexual dimorphism through its interaction with Nkx3.1 in the developing prostate gland...
  6. ncbi The smooth muscle gamma-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor
    J A Carson
    Department of Cellular and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 275:39061-72. 2000
    An evolutionarily conserved vertebrate homologue of the Drosophila NK-3 homeodomain gene bagpipe, Nkx3-1, is expressed in vascular and visceral mesoderm-derived muscle tissues and may influence smooth muscle cell differentiation...
  7. pmc Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis
    H Song
    Department of Pathology and Immunology, School of Medicine, Washington University at St Louis, St Louis, MO 63110, USA
    Oncogene 28:3307-19. 2009
    ..1 loss depend on the epithelial proliferative stage at which its expression is lost, and that alterations in the PTEN-AKT-NKX3.1 axis are important for prostate cancer initiation...
  8. ncbi Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation
    Nan Gao
    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
    Development 132:3431-43. 2005
    ..These data indicate that Foxa1 plays a pivotal role in controlling prostate morphogenesis and cell differentiation...
  9. ncbi Loss-of-function of Nkx3.1 promotes increased oxidative damage in prostate carcinogenesis
    Xuesong Ouyang
    Center for Advanced Biotechnology and Medicine, The Cancer Institute of New Jersey, Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 5638, USA
    Cancer Res 65:6773-9. 2005
    ..Thus, our findings provide a molecular link between a gene whose inactivation is known to be involved in prostate carcinogenesis, namely Nkx3.1, and oxidative damage of the prostatic epithelium...
  10. pmc Distinct regulatory elements mediate the dynamic expression pattern of Nkx3.1
    Hui Chen
    Department of Biological Sciences, University of Maryland Baltimore County, 21250, USA
    Dev Dyn 234:961-73. 2005
    ..1 cis-regulatory elements provides a unique starting point to dissect signaling pathways involved in prostate organogenesis and pathogenesis and provides a system to perturb gene expression throughout prostate development...
  11. pmc NKX3.1 is regulated by protein kinase CK2 in prostate tumor cells
    Xiang Li
    Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA
    Mol Cell Biol 26:3008-17. 2006
    ..1, whereas CK2alpha' liberated from the holoenzyme could not. These data establish CK2 as a regulator of NKX3.1 in prostate tumor cells and provide evidence for functionally distinct pools of CK2alpha' in LNCaP cells...
  12. ncbi NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss
    Qunying Lei
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095, USA
    Cancer Cell 9:367-78. 2006
    ..1 has little effect on Pten wild-type epithelium, suggesting that PTEN plays a predominant role in PTEN-NKX3.1 interplay. Manipulating NKX3.1 expression may serve as a therapeutic strategy for treating PTEN-deficient prostate cancers...
  13. ncbi Emergence of androgen independence at early stages of prostate cancer progression in Nkx3.1; Pten mice
    Hui Gao
    Center for Advanced Biotechnology and Medicine, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cancer Res 66:7929-33. 2006
    ....
  14. ncbi Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice
    Whitney Banach-Petrosky
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
    Cancer Res 67:9089-96. 2007
    ..We propose that exposure to reduced androgens may promote prostate tumorigenesis by selecting for molecular events that promote more aggressive, hormone-refractory tumors...
  15. pmc A causal role for ERG in neoplastic transformation of prostate epithelium
    Olga Klezovitch
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 105:2105-10. 2008
    ..Our data demonstrate that ERG plays an important causal role in the transformation of prostate epithelium and should be considered as a target for prevention or early therapeutic intervention...
  16. pmc Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration
    Xiuping Yu
    Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Prostate 69:249-62. 2009
    ..Although stabilizing mutations in APC and beta-Catenin are rare in primary prostate tumors, recent studies suggest that cytoplasmic/nuclear beta-Catenin is associated with advanced, metastatic, hormone-refractory prostate carcinoma...
  17. pmc NKX3.1 activates expression of insulin-like growth factor binding protein-3 to mediate insulin-like growth factor-I signaling and cell proliferation
    Erin Muhlbradt
    Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA
    Cancer Res 69:2615-22. 2009
    ..Thus, there is a close relationship in vitro and in vivo between NKX3.1 and IGFBP-3. The growth-suppressive effects of NKX3.1 in prostate cells are mediated, in part, by activation of IGFBP-3 expression...
  18. ncbi Tissue-specific expression of murine Nkx3.1 in the male urogenital system
    P J Sciavolino
    Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854 5638, USA
    Dev Dyn 209:127-38. 1997
    ..1 in the growth and development of the prostate and/or other tissues of the male urogenital system, and suggest that Nkx3.1 may play a role in sexually dimorphic as well as non-sexually dimorphic organogenesis...
  19. pmc A luminal epithelial stem cell that is a cell of origin for prostate cancer
    Xi Wang
    Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nature 461:495-500. 2009
    ..These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer...
  20. pmc SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation
    Martin K Thomsen
    Section of Gene Function and Regulation, Institute of Cancer Research, London SW3 6JB, United Kingdom
    Cancer Res 70:979-87. 2010
    ..Our findings identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it promotes tumor cell proliferation...
  21. pmc Loss of Nkx3.1 expression in bacterial prostatitis: a potential link between inflammation and neoplasia
    May Khalili
    Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA
    Am J Pathol 176:2259-68. 2010
    ..These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth...
  22. pmc Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis
    Philip D Anderson
    Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Clin Invest 122:1907-19. 2012
    ..We propose that coregulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism underlying the cooperativity of oncogenic mutations during tumorigenesis...
  23. pmc Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model
    Nicolas Floc'h
    Department of Urology and Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10031, USA
    Cancer Res 72:4483-93. 2012
    ..Our findings suggest that dual targeting of the Akt and mTOR signaling pathways using MK-2206 and ridaforolimus (MK-8669) may be effective for treatment of CRPC, particularly for patients with deregulated Rb pathway activity...
  24. pmc TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation
    Orla M Casey
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e41668. 2012
    ....
  25. pmc Wnt signaling though beta-catenin is required for prostate lineage specification
    Brian W Simons
    Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Biol 371:246-55. 2012
    ..Deletion of beta-catenin in the adult prostate did not significantly affect organ homeostasis. Collectively, these data establish that beta-catenin and Wnt signaling play key roles in prostate lineage specification and bud outgrowth...
  26. pmc Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee
    Michael Ittmann
    Department of Pathology and Immunology, Baylor College of Medicine, Texas 77030, USA
    Cancer Res 73:2718-36. 2013
    ....
  27. pmc ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer
    Alvaro Aytes
    Department of Urology and Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Department of Systems Biology, and Department of Medicine and Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032
    Proc Natl Acad Sci U S A 110:E3506-15. 2013
    ..Our findings indicate that ETV4 promotes metastasis in prostate tumors that have activation of PI3-kinase and Ras signaling, and therefore, ETV4 represents a potential target of therapeutic intervention for metastatic prostate cancer. ..
  28. pmc Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy
    Alvaro Aytes
    Department of Urology, Columbia University Medical Center, New York, NY 10032, USA Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L Hospitalet de Llobregat, Barcelona 08907, Spain
    Cancer Cell 25:638-51. 2014
    ..Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer. ..
  29. pmc Roles for Nkx3.1 in prostate development and cancer
    R Bhatia-Gaur
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 USA
    Genes Dev 13:966-77. 1999
    ..The Nkx3.1 mutant mice provide a unique animal model for examining the relationship between normal prostate differentiation and early stages of prostate carcinogenesis...
  30. pmc Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis
    Minjung J Kim
    Center for Advanced Biotechnology and Medicine and Department of Neuroscience, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 99:2884-9. 2002
    ..Our findings underscore the significance of interactions between tissue-specific regulators such as Nkx3.1 and broad-spectrum tumor suppressors such as Pten in contributing to the distinct phenotypes of different cancers...
  31. ncbi Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis
    Minjung J Kim
    Department of Neuroscience, Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Cancer Res 62:2999-3004. 2002
    ..1 mutant mice accurately model early stages of prostate carcinogenesis. More generally, our tissue recombination assay provides an empirical test to examine the relationship of PIN to prostate carcinoma...
  32. ncbi Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse
    Heike Herbrand
    Department of Cell and Molecular Biology, Technical University of Braunschweig, Spielmann Street 7, 38106 Braunschweig, Germany
    Mech Dev 117:217-24. 2002
    ..1 contributes to the formation of the axial skeleton in addition to the Bapx1 gene. Moreover, both genes seem to collaborate in a yet unknown vital function in the mouse embryo...
  33. pmc A critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis
    Hui Gao
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 101:17204-9. 2004
    ..Our findings suggest that p27(kip1) possesses dosage-sensitive positive as well as negative modulatory roles in prostate cancer progression...
  34. ncbi Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation
    Jeffrey A Magee
    Department of Pathology, Division of Laboratory Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Cancer Cell 3:273-83. 2003
    ..Thus, loss of a single Nkx3.1 allele likely results in hyperplasia and PIN by increasing the probability of completely inactivating select Nkx3.1-regulated pathways within a subset of affected cells...
  35. ncbi Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases
    Cory Abate-Shen
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry, New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Cancer Res 63:3886-90. 2003
    ..We conclude that Nkx3.1(+/-); Pten(+/-) mice recapitulate key features of advanced prostate cancer and represent a useful model for investigating associated molecular mechanisms and for evaluating therapeutic approaches...
  36. ncbi Roles of the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis
    Michael M Shen
    Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Cancer Institute of New Jersey, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Dev Dyn 228:767-78. 2003
    ..Here, we review recent findings concerning the biological as well as biochemical function of this central regulator of prostate development and carcinogenesis...
  37. ncbi Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects of minor salivary glands: parallels to glandular duct morphogenesis in prostate
    A Schneider
    Department of Cell and Molecular Biology, University of Braunschweig, Spielmannstrasse 7, 38106, Braunschweig, Germany
    Mech Dev 95:163-74. 2000
    ..Expression in lung appeared augmented in the absence of Shh. Our results suggest that Nkx3.1 plays a unique role in regulating proliferation of glandular epithelium and in the formation of ducts in prostate and minor salivary glands...
  38. pmc Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia
    Sarki A Abdulkadir
    Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA
    Mol Cell Biol 22:1495-503. 2002
    ..1 allele lose expression of the wild-type allele. Our results support the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this gene in tumor initiation...
  39. ncbi Nkx3.1, a murine homolog of Ddrosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Dev Dyn 219:248-60. 2000
    Nkx3.1 is a homeobox gene related to Drosophila bagpipe. Nkx3...
  40. doi Sox9 is required for prostate development
    Martin K Thomsen
    Section of Gene Function and Regulation, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Dev Biol 316:302-11. 2008
    ..These studies imply that Sox9 is required for the early differentiation of the prostate bud epithelia...
  41. pmc Nkx3.1 binds and negatively regulates the transcriptional activity of Sp-family members in prostate-derived cells
    Steven O Simmons
    Graduate Program in Toxicology and Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA
    Biochem J 393:397-409. 2006
    ..1 DNA-binding activity is itself not required. We conclude that Nkx3.1 negatively regulates Sp-mediated transcription via the tethering of histone deacetylases and/or by inhibiting the association of Sp proteins with co-activators...
  42. pmc RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that promotes tumorigenesis
    Monica Logan
    Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee, USA
    Am J Pathol 183:951-63. 2013
    ..These data provide novel insights into the role of RAMP1 in promoting prostate tumorigenesis and support the potential of RAMP1 as a novel biomarker and possible therapeutic target in prostate cancer. ..
  43. doi ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity
    Feng Jin
    Department of Physiology and Biophysics, Robert Wood Johnson Medical School, UMDNJ, 683 Hoes Lane, Piscataway, New Jersey 08854, USA
    Mol Cancer Res 11:736-47. 2013
    ..Together, these findings suggest that elevated MED1 is a critical molecular event associated with prostate oncogenesis...
  44. pmc MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells
    Tsuyoshi Iwata
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 5:e9427. 2010
    ..We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas...
  45. pmc Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN
    Pankaj Sharma
    Mol Cancer 12:67. 2013
    ..Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology...
  46. pmc Single luminal epithelial progenitors can generate prostate organoids in culture
    Chee Wai Chua
    1 Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA 2 Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA 3 Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA 4 Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Cell Biol 16:951-61, 1-4. 2014
    ..Finally, we provide evidence supporting the feasibility of organoid studies of human prostate tissue. Our studies underscore the progenitor properties of luminal cells, and identify in vitro approaches for studying prostate biology. ..
  47. pmc Atg7 cooperates with Pten loss to drive prostate cancer tumor growth
    Urmila Santanam
    Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA
    Genes Dev 30:399-407. 2016
    ....
  48. pmc SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary
    Sam Goldsmith
    The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Development 143:2376-88. 2016
    ..Therefore, SOX2 has two independent roles during pituitary morphogenesis; firstly, promotion of progenitor proliferation, and subsequently, acquisition of melanotroph identity. ..
  49. doi Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation
    Aditya Dutta
    Departments of Medicine and Urology, Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA
    Science 352:1576-80. 2016
    ..1-G9a-UTY transcriptional regulatory network is essential for prostate differentiation, and we speculate that disruption of such a network predisposes to prostate cancer. ..
  50. pmc Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets of T-cell lymphoblastic leukemia (T-ALL)
    Stefan Nagel
    Department of Human and Animal Cell Lines, Leibniz Institute DSMZ German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
    PLoS ONE 7:e40747. 2012
    ..These results may contribute to the understanding of leukemic transcriptional networks underlying disturbed T-cell differentiation in T-ALL...
  51. pmc Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression
    Ruth L Vinall
    Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Rancho Cordova, CA, USA
    Dis Model Mech 5:914-20. 2012
    ..Further characterization of this model, particularly in a setting of androgen deprivation, should allow further insight into the mechanisms by which the Tp53(R270H) mutation mediates CaP progression...
  52. pmc B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer
    Jingqiang Wang
    Department of Urology and Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10031, USA
    Cancer Res 72:4765-76. 2012
    ..Together, our findings suggest a generalized therapeutic approach to target c-Myc activation in prostate cancer by combinatorial targeting of the PI3K → Akt → mTOR and ERK1/2 MAPK signaling pathways...
  53. pmc Visualization and quantification of mouse prostate development by in situ hybridization
    Kimberly P Keil
    University of Wisconsin Madison, Department of Comparative Biosciences, School of Veterinary Medicine, 1656 Linden Dr Madison, WI 53706, USA
    Differentiation 84:232-9. 2012
    ..We also found that Nkx3-1, Edar, and Wnt10b mark different prostatic bud regions and are likely to be useful in future studies of regional differences in prostatic bud gene expression...
  54. pmc Mash1 expression is induced in neuroendocrine prostate cancer upon the loss of Foxa2
    Aparna Gupta
    Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
    Prostate 73:582-9. 2013
    ..These studies suggest that the TRAMP NE tumors can form in the absence of Foxa2 by an up regulation of Mash1...
  55. pmc Antioxidant treatment promotes prostate epithelial proliferation in Nkx3.1 mutant mice
    Erin E Martinez
    Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    PLoS ONE 7:e46792. 2012
    ..Our findings provide new insight that may help explain the increased prostate cancer risk observed with vitamin E treatment in the SELECT trial and emphasize the need for preclinical studies using accurate models of cancer...
  56. pmc Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development
    Kimberly P Keil
    Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI 53706, USA
    Endocrinology 153:6091-103. 2012
    ....
  57. pmc Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity
    Zhu A Wang
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Cell Biol 15:274-83. 2013
    ..Our results reveal the inherent plasticity of basal cells, and support a model in which different cells of origin generate distinct molecular subtypes of prostate cancer...
  58. ncbi Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1
    Bin Guan
    Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA
    J Biol Chem 283:4834-40. 2008
    ..1. These data establish TOPORS as a negative regulator of NKX3.1 and implicate TOPORS in prostate cancer progression...
  59. ncbi Physical and functional interactions between the prostate suppressor homeoprotein NKX3.1 and serum response factor
    Jeong Ho Ju
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, NW, Washington, DC 20007, USA
    J Mol Biol 360:989-99. 2006
    ..1 and SRF was demonstrated by targeted mutagenesis of an NKX3.1 expression vector in a SMGA reporter assay. The results implicate the NKX3.1 N-terminal region in regulation of transcriptional activity of this tumor suppressor...
  60. pmc Multistep signaling requirements for pituitary organogenesis in vivo
    M Treier
    Howard Hughes Medical Institute, University of California, San Diego, School and Department of Medicine, La Jolla, California 92093 0648 USA
    Genes Dev 12:1691-704. 1998
    ....
  61. ncbi Mediolateral patterning of somites: multiple axial signals, including Sonic hedgehog, regulate Nkx-3.1 expression
    L Kos
    Laboratory of Mammalian Genes and Development, NICHD, NIH, Bethesda, MD 20892, USA
    Mech Dev 70:25-34. 1998
    ....
  62. ncbi Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development
    M Tanaka
    Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Dev Genet 22:239-49. 1998
    In Drosophila, dorsal mesodermal specification is regulated by the homeobox genes tinman and bagpipe. Vertebrate homologs of tinman and bagpipe have been isolated in various species...
  63. ncbi Sequence and chromosomal assignment of human BAPX1, a bagpipe-related gene, to 4p16.1: a candidate gene for skeletal dysplasia
    K I Yoshiura
    Department of Pediatrics, The University of Iowa, Iowa City, Iowa 52242, USA
    Genomics 45:425-8. 1997
    ..They have increasingly been found to be mutated in human birth defect disorders. Sequences of two bagpipe-related genes in the mouse, Nkx-3.1 and Nkx-3.2, have already been reported. Nkx-3...
  64. pmc Myocardin-dependent activation of the CArG box-rich smooth muscle gamma-actin gene: preferential utilization of a single CArG element through functional association with the NKX3.1 homeodomain protein
    Qiang Sun
    Aab Cardiovascular Research Institute of the University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 284:32582-90. 2009
    ..These results demonstrate the ability of MYOCD to discriminate among several juxtaposed CArG elements, presumably through its novel partnership with NKX3.1, to optimally transactivate the human ACTG2 promoter...
  65. pmc Stromal transforming growth factor-beta signaling mediates prostatic response to androgen ablation by paracrine Wnt activity
    VERONICA R PLACENCIO
    Departments of Cancer Biology, Urologic Surgery, and Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
    Cancer Res 68:4709-18. 2008
    ..These studies reveal a novel TGF-beta, androgen, and Wnt paracrine signaling axis that enables prostatic regression of the distal ducts after androgen ablation while supporting proximal duct survival...
  66. ncbi The use of genetically engineered mouse models of prostate cancer for nutrition and cancer chemoprevention research
    Russell D Klein
    Department of Human Nutrition and Cancer Chemoprevention and Support Program, Comprehensive Cancer Center, The Ohio State University, 325 Campbell Hall, Columbus, 43210, USA
    Mutat Res 576:111-9. 2005
    ....
  67. pmc Interaction of Nkx3.1 and p27kip1 in prostate tumor initiation
    Bernard Gary
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 0007, USA
    Am J Pathol 164:1607-14. 2004
    ..Thus Nkx3.1 and p27kip1 regulate prostatic epithelial cell proliferation and tumor initiation by affecting both haploinsufficient and nonhaploinsufficient pathways...
  68. ncbi Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome
    Isabel Rodrigo
    GSF National Research Center for Environment and Health, Institute of Developmental Genetics, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany
    Development 130:473-82. 2003
    ..These results strongly suggest that Bapx1 is a direct target of Pax1 and Pax9. Together, we conclude that Pax1 and Pax9 are required and sufficient for the chondrogenic differentiation of sclerotomal cells...
  69. pmc Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer
    Hui Gao
    Center for Advanced Biotechnology and Medicine, Cancer Institute of New Jersey, and Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 103:14477-82. 2006
    ..We propose that androgen independence emerges by means of epithelial-stromal competition, in which activation of Akt and Erk promotes AR activity in the prostate epithelium while counteracting antagonistic effects of the stroma...
  70. ncbi Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation
    Yu Takahashi
    Cellular and Molecular Toxicology Division, National Institute of Health Sciences, Setagayaku, Tokyo, Japan
    Dev Dyn 236:1484-94. 2007
    ..The present data strongly suggest that patterning events by bHLH-type transcription factors have deep impacts on regional chondrogenic and myogenic differentiation of somitic cells, mainly by means of control of Pax genes...
  71. pmc Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress
    E Ullman
    Cell Death Differ 15:422-5. 2008
  72. doi Role of epithelial cell fibroblast growth factor receptor substrate 2alpha in prostate development, regeneration and tumorigenesis
    Yongyou Zhang
    Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030 3303, USA
    Development 135:775-84. 2008
    ..Thus, the prostate-specific Frs2alpha(cn) mice provide a useful animal model for scrutinizing the molecular mechanisms underlying prostatic development and tumorigenesis...
  73. doi Structural and functional analysis of domains mediating interaction between the bagpipe homologue, Nkx3.1 and serum response factor
    Yan Zhang
    Department of Systems Biology and Translational Medicine, College of Medicine, Texas A and M Health Science Center, College Station, TX 77843 1114, USA
    Exp Biol Med (Maywood) 233:297-309. 2008
    ..1 and SRF that operate in concert with their respective DNA binding domains to mediate functional transcriptional synergy of these factors to regulate SMGA gene activation...
  74. ncbi Expression of the Nkx3.1 homobox gene during pre and postnatal development
    M Tanaka
    Cardiovascular Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Mech Dev 85:179-82. 1999
    We report here the expression pattern of Nkx3.1, a murine homolog of Drosophila bagpipe, in different stages of embryos and in neonates. Nkx3.1 was expressed in paraxial mesoderm at day 7.5 p.c., in the somite by day 8.0 p.c...
  75. pmc Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model
    Carolyn Waugh Kinkade
    Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:3051-64. 2008
    ..We therefore propose that combination therapy targeting AKT/mTOR and ERK MAPK signaling pathways may be an effective treatment for patients with advanced prostate cancer, in particular those with hormone-refractory disease...
  76. pmc FGFR2 in the dental epithelium is essential for development and maintenance of the maxillary cervical loop, a stem cell niche in mouse incisors
    Yongshun Lin
    Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, Texas, USA
    Dev Dyn 238:324-30. 2009
    ..The results suggest that the FGFR2 signaling axis plays a role in maintaining the stem cell niche required for incisor development and lifelong growth...
  77. pmc Prostate-specific Klf6 inactivation impairs anterior prostate branching morphogenesis through increased activation of the Shh pathway
    Ching Ching Leow
    Departments of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA
    J Biol Chem 284:21057-65. 2009
    ..Klf6-deficiency leads to elevated levels of hedgehog pathway components (Shh, Ptc, and Gli) and loss of their localized expression, which in turn causes impaired lateral branching...
  78. ncbi Emx2 is required for growth of the hippocampus but not for hippocampal field specification
    S Tole
    Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, USA
    J Neurosci 20:2618-25. 2000
    ..Thus, Emx2 is required for normal growth and maturation of the hippocampus but not for the specification of cells to particular hippocampal field identities...
  79. pmc Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development
    C Kioussi
    Howard Hughes Medical Institute, University of California San Diego, School, Department of Medicine, 9500 Gilman Drive, Cellular and Molecular Medicine Room 345, La Jolla, CA 92093 0648, USA
    Proc Natl Acad Sci U S A 96:14378-82. 1999
    ..We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals...
  80. doi Defects and rescue of the minor salivary glands in Eda pathway mutants
    K L Wells
    Department of Craniofacial Development, King s College London Dental Institute, London SE1 9RT, UK
    Dev Biol 349:137-46. 2011
    ..Supplementation with Fgf8 or Shh, previously reported targets of Eda signalling, leads to induction of gland like structures in a few cases, but these fail to develop into minor SGs...
  81. ncbi Intronic DNA elements regulate androgen-dependent expression of the murine Nkx3.1 gene
    Chinatsu Kojima
    Department of Systems Biology and Translational Medicine, College of Medicine, Texas A and M Health Science Center, College Station, TX 77843 1114, USA
    Gene Expr 15:89-102. 2010
    ..Taken together, our study shows that androgen-dependent transcription of the mouse Nkx3.1 gene is conferred through a noncanonical element within the intron of the gene...
  82. pmc Differentiation of the ductal epithelium and smooth muscle in the prostate gland are regulated by the Notch/PTEN-dependent mechanism
    Xinyu Wu
    Department of Urology, New York University School of Medicine, 423 East 23rd Street, New York, NY 10010, USA
    Dev Biol 356:337-49. 2011
    ..In addition, we found that both positive and negative modulation of Notch signaling results in abnormal organization of the prostate tissue, and can contribute to prostate disease in the adult organ...
  83. ncbi Genetic contributions of nonautoimmune SWR mice toward lupus nephritis
    S Xie
    Simmon s Arthritis Research Center and Center for Immunology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA
    J Immunol 167:7141-9. 2001
    ..In conclusion, lupus in the SNF(1) strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation...

Research Grants3

  1. Hedgehog Pathway in Urogenital Sinus Development
    David Berman; Fiscal Year: 2005
    ..The aim of the mentored training period is to acquire the necessary intellectual and technical skills to transition into independent investigation of urogenital development and its relationships to urologic disease. ..
  2. Fatty Acid Effects on COX-2 Dependent Prostate Cancer
    Russell Klein; Fiscal Year: 2005
    ..abstract_text> ..
  3. Hedgehog signaling links bladder injury and cancer
    DAVID MONTY BERMAN; Fiscal Year: 2010
    ..4) To test whether continuously enforced Hh signaling is sufficient to induce urothelial carcinogenesis. ..