KISS1 is down-regulated by 17beta-estradiol in MDA-MB-231 cells through a nonclassical mechanism and loss of ribonucleic acid polymerase II binding at the proximal promoter - PubMed (original) (raw)
. 2010 Aug;151(8):3764-72.
doi: 10.1210/en.2010-0260. Epub 2010 Jun 9.
Affiliations
- PMID: 20534720
- DOI: 10.1210/en.2010-0260
KISS1 is down-regulated by 17beta-estradiol in MDA-MB-231 cells through a nonclassical mechanism and loss of ribonucleic acid polymerase II binding at the proximal promoter
Lukas Huijbregts et al. Endocrinology. 2010 Aug.
Abstract
Kisspeptins are hypothalamic neuropeptides encoded by KISS1 and recently described as major regulators of GnRH release from hypothalamic neurons. Although 17beta-estradiol (E2)-induced up-regulation of KISS1 expression has been documented in anteroventral periventricular nucleus neurons, E2 down-regulates KISS1 expression in arcuate nucleus neurons via the estrogen receptor alpha by unknown molecular mechanisms. Because KISS1 was initially described as a metastasis inhibitor, notably in breast tumors, we used the MDA-MB-231 breast cancer cell line, which expresses high levels of KISS1, to characterize the molecular mechanism underlying KISS1 regulation by E2. E2 rapidly down-regulated endogenous KISS1 in a stable ERalpha-expressing MDA-MB-231 cell line. Promoter analysis revealed that E2 down-regulation was determined by a short 93-bp sequence devoid of estrogen response element and Sp1 sites. E2 down-regulation persisted with an ERalpha that was unable to bind DNA and in the presence of histone deacetylase inhibitor. In the absence of E2, unliganded ERalpha and RNA polymerase II (RNAPII) were present on the proximal promoter. E2 stimulation induced recruitment of ERalpha and loss of RNAPII at the proximal promoter. Along the gene body, total RNAPII amounts were similar in E2-treated and untreated cells, whereas the active form was significantly less abundant in E2-treated cells. Thus, E2-induced down-regulation of KISS1 is mediated by a pathway combining RNAPII loss at the proximal promoter and modulation of active RNAPII along the gene body, which is a novel mechanism in the complex process of E2-induced repression of gene expression.
Similar articles
- Estrogen regulates KiSS1 gene expression through estrogen receptor alpha and SP protein complexes.
Li D, Mitchell D, Luo J, Yi Z, Cho SG, Guo J, Li X, Ning G, Wu X, Liu M. Li D, et al. Endocrinology. 2007 Oct;148(10):4821-8. doi: 10.1210/en.2007-0154. Epub 2007 Jul 26. Endocrinology. 2007. PMID: 17656465 - High tumoral levels of Kiss1 and G-protein-coupled receptor 54 expression are correlated with poor prognosis of estrogen receptor-positive breast tumors.
Marot D, Bieche I, Aumas C, Esselin S, Bouquet C, Vacher S, Lazennec G, Perricaudet M, Kuttenn F, Lidereau R, de Roux N. Marot D, et al. Endocr Relat Cancer. 2007 Sep;14(3):691-702. doi: 10.1677/ERC-07-0012. Endocr Relat Cancer. 2007. PMID: 17914099 - Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters.
Kininis M, Chen BS, Diehl AG, Isaacs GD, Zhang T, Siepel AC, Clark AG, Kraus WL. Kininis M, et al. Mol Cell Biol. 2007 Jul;27(14):5090-104. doi: 10.1128/MCB.00083-07. Epub 2007 May 21. Mol Cell Biol. 2007. PMID: 17515612 Free PMC article. - Regulation of KiSS1 gene expression.
Li D, Yu W, Liu M. Li D, et al. Peptides. 2009 Jan;30(1):130-8. doi: 10.1016/j.peptides.2008.09.025. Epub 2008 Oct 17. Peptides. 2009. PMID: 18996159 Review. - KiSS1 in regulation of metastasis and response to antitumor drugs.
Corno C, Perego P. Corno C, et al. Drug Resist Updat. 2019 Jan;42:12-21. doi: 10.1016/j.drup.2019.02.001. Epub 2019 Feb 11. Drug Resist Updat. 2019. PMID: 30776659 Review.
Cited by
- KISS1 and Kisspeptins Detection in Cell Lines.
Harihar S. Harihar S. Methods Mol Biol. 2024;2811:177-184. doi: 10.1007/978-1-0716-3882-8_13. Methods Mol Biol. 2024. PMID: 39037658 - Inverse Correlation of KISS1 and KISS1R Expression in Triple-negative Breast Carcinomas from African American Women.
Qasim M, Ricks-Santi LJ, Naab TJ, Rajack F, Beyene D, Abbas M, Kassim OO, Copeland RL, Kanaan Y. Qasim M, et al. Cancer Genomics Proteomics. 2022 Nov-Dec;19(6):673-682. doi: 10.21873/cgp.20350. Cancer Genomics Proteomics. 2022. PMID: 36316037 Free PMC article. - KISS1 in metastatic cancer research and treatment: potential and paradoxes.
Ly T, Harihar S, Welch DR. Ly T, et al. Cancer Metastasis Rev. 2020 Sep;39(3):739-754. doi: 10.1007/s10555-020-09868-9. Cancer Metastasis Rev. 2020. PMID: 32152912 Free PMC article. Review. - Role of the tumor microenvironment in regulating the anti-metastatic effect of KISS1.
Harihar S, Ray S, Narayanan S, Santhoshkumar A, Ly T, Welch DR. Harihar S, et al. Clin Exp Metastasis. 2020 Apr;37(2):209-223. doi: 10.1007/s10585-020-10030-6. Epub 2020 Feb 22. Clin Exp Metastasis. 2020. PMID: 32088827 Free PMC article. Review. - A Multi-Oscillatory Circadian System Times Female Reproduction.
Simonneaux V, Bahougne T. Simonneaux V, et al. Front Endocrinol (Lausanne). 2015 Oct 20;6:157. doi: 10.3389/fendo.2015.00157. eCollection 2015. Front Endocrinol (Lausanne). 2015. PMID: 26539161 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous