Genomes and Genes
Summary: Isoforms encoded by the WT1 Wilms tumor suppressor gene (GENES, WILMS TUMOR) and produced by alternative splicings. They are zinc finger-containing transcription factors involved in both transactivation and repression, and are critical for normal development and function of the urogenital tract.
- Dai C, Saleem M, Holzman L, Mathieson P, Liu Y. Hepatocyte growth factor signaling ameliorates podocyte injury and proteinuria. Kidney Int. 2010;77:962-73 pubmed publisher..Collectively, these results indicate that HGF/c-met signaling has an important role in protecting podocytes from injury, thereby reducing proteinuria. ..
- Gregg J, Brown K, Mintz E, Piontkivska H, Fraizer G. Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection. BMC Cancer. 2010;10:165 pubmed publisher..The relevance of WT1 expression in prostate cancer was confirmed by analysis of tumor tissue and cell lines, suggesting a potential role for WT1 in prostate tumorigenesis. ..
- Nascimento F, Ceciliano T, Aguila M, Mandarim de Lacerda C. Maternal vitamin D deficiency delays glomerular maturity in F1 and F2 offspring. PLoS ONE. 2012;7:e41740 pubmed publisher..These findings demonstrate that maternal vitamin D deficiency accompanies changes in the renal expression of important factors that may retard the maturation of glomeruli by extending the period of nephrogenesis. ..
- Yoon J, Kim H, Shin S, Yahng S, Lee S, Cho B, et al. Serial measurement of WT1 expression and decrement ratio until hematopoietic cell transplantation as a marker of residual disease in patients with cytogenetically normal acute myelogenous leukemia. Biol Blood Marrow Transplant. 2013;19:958-66 pubmed publisher..These measures may be applied throughout the course of treatment and even after HSCT. ..
- Maslak P, Dao T, Krug L, Chanel S, Korontsvit T, Zakhaleva V, et al. Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood. 2010;116:171-9 pubmed publisher..Further studies are needed to establish the role of vaccination as viable postremission therapy for acute myeloid leukemia. ..
- Martínez Estrada O, Lettice L, Essafi A, Guadix J, Slight J, Velecela V, et al. Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet. 2010;42:89-93 pubmed publisher..These new insights into the molecular mechanisms regulating cardiovascular progenitor cells and EMT will shed light on the pathogenesis of heart diseases and may help the development of cell-based therapies. ..
- Krug L, Dao T, Brown A, Maslak P, Travis W, Bekele S, et al. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. Cancer Immunol Immunother. 2010;59:1467-79 pubmed publisher..This multivalent WT1 peptide analog vaccine induces immune responses in a high proportion of patients with thoracic malignancies with minimal toxicity. A randomized trial testing this vaccine as adjuvant therapy in MPM is planned. ..
- Rezvani K, Yong A, Mielke S, Jafarpour B, Savani B, Le R, et al. Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies. Haematologica. 2011;96:432-40 pubmed publisher..New approaches are needed to induce long-term high-avidity memory responses against leukemia antigens. ..
- Van Tendeloo V, van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010;107:13824-9 pubmed publisher..These data support the further development of vaccination with WT1 mRNA-loaded dendritic cells as a postremission treatment to prevent full relapse in AML patients. ..
- Chau Y, Hastie N. The role of Wt1 in regulating mesenchyme in cancer, development, and tissue homeostasis. Trends Genet. 2012;28:515-24 pubmed publisher..We believe that future studies aimed at elucidating the mechanisms underlying the functions of Wt1 in adult cells will reveal key cell types, pathways, and molecules regulating adult tissue homeostasis and repair...
- Hayashi S, Oji Y, Kanai Y, Teramoto T, Kitaichi M, Kawaguchi T, et al. Low Wilms' tumor gene expression in tumor tissues predicts poor prognosis in patients with non-small-cell lung cancer. Cancer Invest. 2012;30:165-71 pubmed publisher..Cox analysis revealed that the gene level was a significant prognostic factor in OS and DFS. Low WT1 expression predicted poor prognosis in patients with NSCLC. ..
- Lee H, Han K, Lee S, Kim S, Kang H, Cheong H. Urinary exosomal WT1 in childhood nephrotic syndrome. Pediatr Nephrol. 2012;27:317-20 pubmed publisher..The remaining 12 (30%) were steroid-resistant, including 8 with FSGS and 4 with MCNS. Urinary exosomes were isolated by a differential centrifugation method, and WT1 was measured by Western blot analysis...
- ..We conclude that claims of a cardiomyocyte fate of epicardial cells in the mouse are not substantiated. ..
- Gao S, Xing C, Chen C, Lin S, Dong P, Yu F. miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level. J Exp Clin Cancer Res. 2011;30:110 pubmed publisher..However the mechanism of inhibiting the proliferation of leukemic cells is poorly understood...
- Zeng B, Ren X, Cao F, Zhou X, Zhang J. Developmental patterns and characteristics of epicardial cell markers Tbx18 and Wt1 in murine embryonic heart. J Biomed Sci. 2011;18:67 pubmed publisher..5 to at least E14.5, and Wt1 is expressed within the heart from E12.5 to at least E14.5, but not in the cardiomyocyte. These findings may provide new insights on the role of the epicardial cells in cardiac regeneration. ..
- von Gise A, Zhou B, Honor L, Ma Q, Petryk A, Pu W. WT1 regulates epicardial epithelial to mesenchymal transition through ?-catenin and retinoic acid signaling pathways. Dev Biol. 2011;356:421-31 pubmed publisher..Collectively, our study shows that Wt1 regulates epicardial EMT and heart development through canonical Wnt, non-canonical Wnt, and retinoic acid signaling pathways. ..
- Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, et al. Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res. 2009;69:9003-11 pubmed publisher..In consequence, the vector-transduced lymphocytes showed enhanced cytotoxic activity against antigen-expressing tumor cells. Therefore, our novel TCR gene therapy may open a new gate for effective immunotherapy in cancer patients. ..
- Vicent S, Chen R, Sayles L, Lin C, Walker R, Gillespie A, et al. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest. 2010;120:3940-52 pubmed publisher..These findings reveal an unexpected role for WT1 as a key regulator of the genetic network of oncogenic KRAS and provide important insight into the mechanisms that regulate proliferation or senescence in response to oncogenic signals. ..
- Semsri S, Krig S, Kotelawala L, Sweeney C, Anuchapreeda S. Inhibitory mechanism of pure curcumin on Wilms' tumor 1 (WT1) gene expression through the PKC? signaling pathway in leukemic K562 cells. FEBS Lett. 2011;585:2235-42 pubmed publisher..Our study indicates that pure curcumin attenuates WT1 auto-regulatory function through inhibition of PKC? signaling in K562 cells. ..
- Cano E, Carmona R, Muñoz Chápuli R. Wt1-expressing progenitors contribute to multiple tissues in the developing lung. Am J Physiol Lung Cell Mol Physiol. 2013;305:L322-32 pubmed publisher..Our results suggest a novel role for the embryonic mesothelium-derived cells in lung morphogenesis and involve the Wilms' tumor suppressor gene in the development of this organ. ..
- Hartkamp J, Carpenter B, Roberts S. The Wilms' tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Mol Cell. 2010;37:159-71 pubmed publisher..Our findings provide insights into the function of HtrA2 in the regulation of apoptosis and the oncogenic activities of WT1. ..
- Green L, Wagner K, Campbell H, Addison K, Roberts S. Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiation. Nucleic Acids Res. 2009;37:431-40 pubmed publisher..We provide evidence that the regulation of BASP1 promoter occupancy involves the sumoylation of BASP1. Our results reveal a dynamic cooperation between WT1 and BASP1 in the regulation of gene expression during differentiation. ..
- May R, Dao T, Pinilla Ibarz J, Korontsvit T, Zakhaleva V, Zhang R, et al. Peptide epitopes from the Wilms' tumor 1 oncoprotein stimulate CD4+ and CD8+ T cells that recognize and kill human malignant mesothelioma tumor cells. Clin Cancer Res. 2007;13:4547-55 pubmed..These studies provide the rationale for using the WT1 CD4(+) peptides in conjunction with CD8(+) peptide epitopes to vaccinate patients with WT1-expressing cancers. ..
- Oka Y, Tsuboi A, Kawakami M, Elisseeva O, Nakajima H, Udaka K, et al. Development of WT1 peptide cancer vaccine against hematopoietic malignancies and solid cancers. Curr Med Chem. 2006;13:2345-52 pubmed..The power of TAA-derived cancer vaccine may be enhanced by combination with stronger adjuvants, helper peptide, or conventional treatments such as molecular-target-based drugs. ..
- Tatsumi N, Oji Y, Tsuji N, Tsuda A, Higashio M, Aoyagi S, et al. Wilms' tumor gene WT1-shRNA as a potent apoptosis-inducing agent for solid tumors. Int J Oncol. 2008;32:701-11 pubmed..The results presented here demonstrated that WT1-shRNA targeting exon 5 should serve as a potent anti-cancer agent for various types of solid tumors. ..
- Wilm B, Ipenberg A, Hastie N, Burch J, Bader D. The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development. 2005;132:5317-28 pubmed..Our data reveal a conserved mechanism in blood vessel formation to coelomic organs, and have major implications for our understanding of vertebrate organogenesis and vascular deficiencies of the gut. ..
- Boublikova L, Kalinova M, Ryan J, Quinn F, O Marcaigh A, Smith O, et al. Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring. Leukemia. 2006;20:254-63 pubmed..Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse. ..
- Netinatsunthorn W, Hanprasertpong J, Dechsukhum C, Leetanaporn R, Geater A. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. BMC Cancer. 2006;6:90 pubmed..The HR for recurrence-free survival was not confounded by any other variables. This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma. ..
- Steinbach D, Schramm A, Eggert A, Onda M, Dawczynski K, Rump A, et al. Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia. Clin Cancer Res. 2006;12:2434-41 pubmed..Notably, some of these markers could also serve as therapeutic targets or might be involved in leukemogenesis. MSLN is already used as a target for immunotherapy in clinical trials in other malignancies. ..
- Srivastava A, Fuchs B, Zhang K, Ruan M, Halder C, Mahlum E, et al. High WT1 expression is associated with very poor survival of patients with osteogenic sarcoma metastasis. Clin Cancer Res. 2006;12:4237-43 pubmed..WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis. ..
- Hohenstein P, Hastie N. The many facets of the Wilms' tumour gene, WT1. Hum Mol Genet. 2006;15 Spec No 2:R196-201 pubmed
- Keilholz U, Menssen H, Gaiger A, Menke A, Oji Y, Oka Y, et al. Wilms' tumour gene 1 (WT1) in human neoplasia. Leukemia. 2005;19:1318-23 pubmed..This report reviews the current knowledge on the role of WT1 in tumour promotion and as a diagnostic and therapeutic target, and summarizes the data presented and discussed in this meeting. ..
- King Underwood L, Little S, Baker M, Clutterbuck R, Delassus S, Enver T, et al. Wt1 is not essential for hematopoiesis in the mouse. Leuk Res. 2005;29:803-12 pubmed..We conclude that Wt1 is not essential for murine hematopoiesis and that there may be significant differences in its role between mouse and man. ..
- Wagner N, Wagner K, Scholz H, Kirschner K, Schedl A. Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms' tumor suppressor Wt1. Am J Physiol Regul Integr Comp Physiol. 2006;291:R779-87 pubmed..Our results show that nestin is expressed at different stages of kidney and cardiac development and suggest that its expression in these organs might be regulated by the Wilms' tumor suppressor Wt1. ..
- Morrison A, Viney R, Ladomery M. The post-transcriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta. 2008;1785:55-62 pubmed..WT1's first reported post-transcriptional function is also reviewed. WT1's complex roles in development and disease now need to be understood in terms of both DNA and mRNA targets. ..
- Jacobsohn D, Tse W, Chaleff S, Rademaker A, Duerst R, Olszewski M, et al. High WT1 gene expression before haematopoietic stem cell transplant in children with acute myeloid leukaemia predicts poor event-free survival. Br J Haematol. 2009;146:669-74 pubmed publisher..A larger prospective study is warranted to compare the value of high WT1 expression and other markers of minimal residue disease in predicting clinical outcomes after HSCT. ..
- Burwell E, McCarty G, Simpson L, Thompson K, Loeb D. Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells. Oncogene. 2007;26:3423-30 pubmed
- Hinkes B, Mucha B, Vlangos C, Gbadegesin R, Liu J, Hasselbacher K, et al. Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2). Pediatrics. 2007;119:e907-19 pubmed..Fourth, there are most likely additional unknown genes mutated in early-onset nephrotic syndrome. ..
- Jomgeow T, Oji Y, Tsuji N, Ikeda Y, Ito K, Tsuda A, et al. Wilms' tumor gene WT1 17AA(-)/KTS(-) isoform induces morphological changes and promotes cell migration and invasion in vitro. Cancer Sci. 2006;97:259-70 pubmed..The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions. ..
- Stoll R, Lee B, Debler E, Laity J, Wilson I, Dyson H, et al. Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA. J Mol Biol. 2007;372:1227-45 pubmed..The mutations are of two types, and either destabilize the zinc finger structure or replace key base contact residues. ..
- Gbadegesin R, Hinkes B, Hoskins B, Vlangos C, Heeringa S, Liu J, et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008;23:1291-7 pubmed..If this observation is confirmed in a larger study, mutations in PLCE1 may serve as a biomarker for selecting patients with IDMS who may benefit from treatment. ..
- Wagner N, Wagner K, Theres H, Englert C, Schedl A, Scholz H. Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1. Genes Dev. 2005;19:2631-42 pubmed..These findings demonstrate that transcriptional activation of the TrkB neurotrophin receptor gene by the Wilms' tumor suppressor Wt1 is a crucial mechanism for normal vascularization of the developing heart. ..
- Cilloni D, Gottardi E, Saglio G. WT1 overexpression in acute myeloid leukemia and myelodysplastic syndromes. Methods Mol Med. 2006;125:199-211 pubmed..In this chapter, we describe the method for the quantification of WT1 transcript by real-time polymerase chain reaction. ..
- Austin A, Compton L, Love J, Brown C, Barnett J. Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFbeta. Dev Dyn. 2008;237:366-76 pubmed publisher..These data demonstrate that TGFbeta induces epicardial cell differentiation and that immortalized epicardial cells provide a suitable model for differentiation. ..
- Murphy A, Viero S, Ho M, Thorner P. Diagnostic utility of nestin expression in pediatric tumors in the region of the kidney. Appl Immunohistochem Mol Morphol. 2009;17:517-23 pubmed publisher..Nestin reactivity may be useful in differentiating Wilms tumor from Ewing sarcoma, renal cell carcinoma, or nestin-negative clear cell sarcoma. ..