Research Topics
Genomes and Genes | CAROLYN KLINGESummaryAffiliation: University of Louisville Country: USA Publications
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Publications
Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cellsWasana K Sumanasekera
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY 40292, USA
Cell Tissue Res 324:243-53. 2006....
miRNAs and estrogen actionCarolyn M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Trends Endocrinol Metab 23:223-33. 2012..The role of estrogen-regulated miRNA expression, the target genes of these miRNAs, and the role of miRNAs in health and disease is a 'hot' area of research that will yield new insight into molecular mechanisms of estrogen action...
Inhibition of non-small-cell lung cancer growth by combined fulvestrant and vandetanibCarolyn M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Future Oncol 8:529-33. 2012..These preclinical data provide rationale for a clinical trial to test efficacy in NSCLC patients...
Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and estrogen receptor transcriptional activity in lung adenocarcinoma cellsCarolyn M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Mol Cancer Ther 10:2062-71. 2011..These results indicate MUC1-ER functional interaction in lung adenocarcinoma cells and that inhibiting MUC1 inhibits lung adenocarcinoma cell viability...
Estrogenic control of mitochondrial function and biogenesisCarolyn M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
J Cell Biochem 105:1342-51. 2008..Overall, we are just beginning to evaluate the many direct and indirect effects of estrogens on mitochondrial activities...
Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cellsCarolyn M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
FASEB J 22:2185-97. 2008..This study provides important new insights into mechanisms for the beneficial effects of resveratrol in ECs...
Ligand-dependent differences in estrogen receptor beta-interacting proteins identified in lung adenocarcinoma cells corresponds to estrogenic responsesMm Ivanova
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, 40292 USA
Proteome Sci 9:60. 2011..abstract:..
Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cellsCarolyn M Klinge
Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Kentucky 40292, USA
J Biol Chem 280:7460-8. 2005..These data suggest that ER may play a role in the rapid effects of resveratrol in EC and that some of the atheroprotective effects of resveratrol may be mediated through rapid activation of ER signaling in EC...
Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors alpha and beta by coactivators and corepressorsC M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
J Mol Endocrinol 33:387-410. 2004..These data demonstrated that the ERE sequence impacts estradiol-and 4-hydroxytamoxifen-occupied ERalpha and ERbeta interaction with coregulators as measured by transcriptional activity in mammalian cells...
Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcriptionCarolyn M Klinge
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Mol Cell Endocrinol 323:268-76. 2010..Established miR-21 targets PTEN and PDCD4 were reduced in ERalpha46-transfected, E(2)-treated MCF-7 cells. In conclusion, ERalpha46 appears to enhance endocrine responses by inhibiting selected ERalpha66 responses...
The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cellsCarolyn M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
Endocrinology 143:853-67. 2002..These results identify SHP as novel target for blocking 4-OHT agonist activity in endometrial cells...
Estrogen receptor interaction with estrogen response elementsC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
Nucleic Acids Res 29:2905-19. 2001....
Estrogen receptor binding to estrogen response elements slows ligand dissociation and synergistically activates reporter gene expressionC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, KY 40292, USA
Mol Cell Endocrinol 150:99-111. 1999..Since the number of copies of EREc38 did not alter E2 dissociation kinetics, functional synergy must involve cellular factors in addition to the ER ligand...
The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elementsC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, KY 40292, USA
Mol Cell Endocrinol 157:105-19. 1999..We propose that at least part of the mechanism by which the AHR/ARNT complex inhibits estrogen action is by competitively inhibiting ER alpha binding to imperfect ERE sites, adjacent to or overlapping XREs...
The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1C M Klinge
Department of Biochemistry, University of Louisville School of Medicine, Louisville, Kentucky, 40292, USA
Arch Biochem Biophys 373:163-74. 2000....
Estrogen response element sequence impacts the conformation and transcriptional activity of estrogen receptor alphaC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
Mol Cell Endocrinol 174:151-66. 2001..Our results support the hypothesis that the ERE sequence acts as an allosteric effector, altering ER conformation. We speculate that ERE-induced alterations in ERalpha conformation modulate interaction with co-regulatory proteins...
Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT)C M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
Arch Biochem Biophys 390:64-70. 2001..SHP inhibited AHR/ARNT-DNA binding in vitro. These results identify ARNT as a novel SHP target. We speculate a role for SHP in the suppression of agonist-activated AHR/ARNT activity...
Role of estrogen receptor ligand and estrogen response element sequence on interaction with chicken ovalbumin upstream promoter transcription factor (COUP-TF)C M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, KY 40292, USA
J Steroid Biochem Mol Biol 71:1-19. 1999..We suggest that COUP-TFI plays a role in mitigating estrogen-responsive gene expression...
Estrogen response element binding induces alterations in estrogen receptor-alpha conformation as revealed by susceptibility to partial proteolysisT L Ramsey
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
J Mol Endocrinol 27:275-92. 2001..We hypothesize that ERE-induced alterations in ERalpha conformation modulate interaction with coregulatory proteins, resulting in synergistic transcriptional activation...
Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and betaJ L Bowers
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Kentucky 40292, USA
Endocrinology 141:3657-67. 2000..In contrast, resveratrol shows no E2 antagonist activity with ERbeta. These data indicate that resveratrol differentially affects the transcriptional activity of ERalpha and ERbeta in an ERE sequence-dependent manner...
Estrogen receptors alpha and beta exhibit different estradiol and estrogen response element binding in the presence of nonspecific DNAV V Tyulmenkov
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
Arch Biochem Biophys 390:253-64. 2001..We speculate that interaction of ER with genomic DNA may contribute to ER activation and play a role in the observed differences in transcriptional activity of ER alpha and ER beta...
A mathematical approach to predict the affinity of estrogen receptors alpha and beta binding to DNAV V Tyulmenkov
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
Mol Cell Endocrinol 182:109-19. 2001..The equations developed here can be used to screen the promoters of estrogen-responsive genes for candidate ERE sequences...
Response element sequence modulates estrogen receptor alpha and beta affinity and activityP C Kulakosky
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
J Mol Endocrinol 29:137-52. 2002....
hsp70 is not required for high affinity binding of purified calf uterine estrogen receptor to estrogen response element DNA in vitroC M Klinge
Department of Biochemistry, The University of Louisville School of Medicine, KY 40292, USA
J Steroid Biochem Mol Biol 63:283-301. 1997..Additionally, once ER is activated and bound by ligand, the receptor assumes its proper tertiary structure, and hsp70 does not impact ER ligand binding domain conformation...
Chicken ovalbumin upstream promoter-transcription factor interacts with estrogen receptor, binds to estrogen response elements and half-sites, and inhibits estrogen-induced gene expressionC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
J Biol Chem 272:31465-74. 1997....
Binding of type II nuclear receptors and estrogen receptor to full and half-site estrogen response elements in vitroC M Klinge
Department of Biochemistry, The University of Louisville School of Medicine, Louisville, KY 40292, USA
Nucleic Acids Res 25:1903-12. 1997....
Comparison of tamoxifen ligands on estrogen receptor interaction with estrogen response elementsC M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, KY 40292, USA
Mol Cell Endocrinol 143:79-90. 1998..These findings indicate that the behavior of the ER liganded by TAM is generally similar to that of the antiestrogen 4-OHT...
Tamoxifen increases nuclear respiratory factor 1 transcription by activating estrogen receptor beta and AP-1 recruitment to adjacent promoter binding sitesMargarita M Ivanova
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
FASEB J 25:1402-16. 2011..Overall, NRF-1 expression and activity is regulated by 4-OHT via endogenous ERβ in MCF-7 cells...
Anacardic acid inhibits estrogen receptor alpha-DNA binding and reduces target gene transcription and breast cancer cell proliferationDavid J Schultz
Department of Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
Mol Cancer Ther 9:594-605. 2010..These data indicate that AnAc 24:1(omega5) inhibits cell proliferation, cell cycle progression, and apoptosis in an ER-dependent manner by reducing ER-DNA interaction and inhibiting ER-mediated transcriptional responses...
Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cellsMargarita M Ivanova
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Am J Respir Cell Mol Biol 42:320-30. 2010..Together, our results indicate that nuclear localization of P-ser118-ER alpha provides one explanation for sex-dependent differences in E(2)-genomic responses in lung adenocarcinoma cell lines...
Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor betaVeena Vijayanathan
Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 125 Paterson Street, NB, NJ 08903, USA
Biochem Cell Biol 85:1-10. 2007..The increased thermal stability of HT-ERbeta-ERE was associated with reduced specificity of ERbeta-ERE recognition, illustrating profound differences in conformational states of ERbeta induced by E2 and HT...
Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activityWasana K Sumanasekera
Dept of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, KY 40292, USA
Am J Physiol Cell Physiol 293:C566-73. 2007..These data temporally separate E(2) and DHT effects in HUVEC and provide evidence for the possible protective roles of sex steroids on EC function after brief exposure to low hypergravity...
Estrogen receptor beta yield from baculovirus lytic infection is higher than from stably transformed Sf21 cellsMargarita M Ivanova
Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Appl Microbiol Biotechnol 74:1256-63. 2007..We conclude that baculovirus infection of Sf21 cells is better for human ERbeta production than stable-transformation of Sf21 cells...
Maximizing production of estrogen receptor beta with the baculovirus expression systemPeter C Kulakosky
University of Louisville School of Medicine, Louisville, KY, USA
Biotechniques 34:334-8, 340-3. 2003..Baculovirus expressed ER beta-bound EREs with high affinity in a DNA sequence-dependent manner. We conclude that Sf21 cells are the best-suited cells for ER beta production...
Estrogenic activity in white and red wine extractsCarolyn M Klinge
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
J Agric Food Chem 51:1850-7. 2003..Chemical analysis clearly showed that the trans-resveratrol content of the red wine extracts was 1 order of magnitude below the detection limit for YES assay...
Identification of estrogen receptor beta expression in Chinese hamster ovary (CHO) cells and comparison of estrogen-responsive gene transcription in cells adapted to serum-free mediaPadmaja B Thomas
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
J Steroid Biochem Mol Biol 86:41-55. 2003..In conclusion, growing CHO-K1 in serum-free medium does not impact the estrogen responsiveness and this cell line expresses functional ERbeta...
Estrogen receptor beta isoforms exhibit differences in ligand-activated transcriptional activity in an estrogen response element sequence-dependent mannerTimothy L Ramsey
Department of Biochemistry, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Kentucky 40202, USA
Endocrinology 145:149-60. 2004..Collectively, these data indicate that the cellular expression of ERbeta isoforms may differentially impact ERE-regulated target gene expression in a ligand-dependent manner...
Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesisKathleen A Mattingly
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 580 South Preston Street, Louisville, Kentucky 40202, USA
Mol Endocrinol 22:609-22. 2008..Knockdown of NRF-1 blocked E(2) stimulation of mitochondrial biogenesis and activity, indicating a mechanism by which estrogens regulate mitochondrial function by increasing NRF-1 expression...
Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cellsSusan M Dougherty
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
Endocr Relat Cancer 13:113-34. 2006..DRIP205 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males...
Decreased chicken ovalbumin upstream promoter transcription factor II expression in tamoxifen-resistant breast cancer cellsKrista A Riggs
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA
Cancer Res 66:10188-98. 2006..These data indicate that reduced COUP-TFII expression correlates with acquired TAM resistance in human breast cancer cell lines and that COUP-TFII plays a role in regulating the growth inhibitory activity of TAM in breast cancer cells...
A new luciferase reporter gene assay for the detection of androgenic and antiandrogenic effects based on a human prostate specific antigen promoter and PC3/AR human prostate cancer cellsRyoichi Kizu
Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920 0934, Japan
Anal Sci 20:55-9. 2004..We developed the first assay system, in which the expression of luciferase was driven by the promoter of a prostate-specific antigen gene, a typical human androgen-regulated gene...
Transcription profiling of estrogen target genes in young and old mouse uterusAbdelnaby Khalyfa
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 570 South Preson St Baxter Building RM. 304, Louisville, KY 40292, USA
Exp Gerontol 38:1087-99. 2003....
Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cellsRyoichi Kizu
Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920 0934, Japan
Toxicol Sci 76:299-309. 2003....
Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cellsWasana K Sumanasekera
Department of Biochemistry and Molecular Biology and The Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
Toxicol Lett 174:61-73. 2007..These data are the first characterization of rapid effects of DEPE in human EC and may indicate mechanisms for diesel exhaust in vascular function...
Antiandrogenic activity of extracts of diesel exhaust particles emitted from diesel-engine truck under different engine loads and speedsKazumasa Okamura
Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan
Toxicology 195:243-54. 2004..In conclusion, the antiandrogenic effects of DEPE samples were enhanced by a higher engine load which resulted in DEPC samples with elevated AhR agonistic and AR antagonistic activities...
Research Grants
- Regulation of miRNA expression in breast cancer cellsCAROLYN KLINGE; Fiscal Year: 2007..It is our long term hope that miRNAs may provide novel biomarkers and new insights into the mechanisms by which breast tumors gain TAM/antiestrogen-resistance and become invasive and metastatic. ..
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCAROLYN KLINGE; Fiscal Year: 2009....
- Regulation of miRNA in breast cancerCarolyn M Klinge; Fiscal Year: 2010....
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCAROLYN KLINGE; Fiscal Year: 2009....
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCarolyn M Klinge; Fiscal Year: 2010....
- Summer Endocrine Research Training ProgramCAROLYN KLINGE; Fiscal Year: 2007..years the University of Louisville has increased its commitment to health science research and infrastructure, graduate education, and minority recruitment, making this short-term training program for medical students particularly timely ..
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCAROLYN KLINGE; Fiscal Year: 2006..Results will define the molecular mechanisms of ERalpha, ERbeta, and ERalpha/beta heterodimers as transcriptional regulators, with emphasis on the action of antiestrogens. ..
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCAROLYN KLINGE; Fiscal Year: 2002....
- DNA SEQUENCES IMPACT ESTROGEN AND ANTIESTROGEN ACTIVITYCarolyn M Klinge; Fiscal Year: 2010....
