EZH2 participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1

Cancer Biology & Therapy
Tao LiZ Wang

Abstract

Aberrant overexpression of the enhancer of zeste homolog 2 (EZH2), a histone methyltransferase inhibiting targets expression via epigenetic mechanisms, is associated with an invasive phenotype and drug resistance in ovarian cancer. Breast cancer 1 (BRCA1) gene is a well-recognized tumor suppressor, whose downregulation plays a key role in the development of ovarian cancer. In the present study, we found depletion of EZH2 increased BRCA1 protein expression and promoted its nuclear translocation, but decreased BRCA1 mRNA expression. Treatment with the Akt-1 activator insulin-like growth factor-1 (IGF-1) prevented EZH2-induced BRCA1 nuclear/cytoplasmic shuttling. Loss of BRCA1 partially rescued the effects of EZH2 downregulation on proliferation, G 2/M transition, and migration in ovarian cancer cells. However, in a cisplatin-resistant sub-line of A2780 (A2780/DDP), both EZH2 and BRCA1 were overexpressed compared with parental A2780 cells and depletion of EZH2 reduced BRCA1 expression at both mRNA and protein levels. Downregulation of EZH2 or BRCA1 sensitized A2780/DDP cells to cisplatin, whereas simultaneous inhibition of them only resulted in modest resensitization instead of showing any synergistic effect because EZH2 expressio...Continue Reading

References

Apr 5, 1996·Science·R ScullyD M Livingston
Feb 18, 1999·Molecular and Cellular Biology·S P GygiR Aebersold
Jul 18, 2000·International Journal of Cancer. Journal International Du Cancer·P A RussellS A Gayther
Apr 21, 2001·Molecular and Cellular Biology·B XuM B Kastan
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 4, 2002·Molecular & Cellular Proteomics : MCP·Guoan ChenDavid G Beer
Aug 15, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Charlotte Moss, Stan B Kaye
Oct 11, 2002·Nature·Sooryanarayana VaramballyArul M Chinnaiyan
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
Dec 8, 2005·Neoplasia : an International Journal for Oncology Research·Michael ZeidlerCelina G Kleer
Dec 17, 2005·Nature·Emmanuelle ViréFrançois Fuks
Apr 10, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sining Chen, Giovanni Parmigiani
Mar 18, 2008·Biochemical and Biophysical Research Communications·Yang WangQimin Zhan
Apr 24, 2008·The Journal of Biological Chemistry·Satoshi FujiiAtsushi Ochiai
Dec 23, 2008·Cell Cycle·Amber YasmeenAla-Eddin Al Moustafa
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jer-Yen Yang, Mien-Chie Hung
Apr 6, 2011·Breast Cancer Research and Treatment·Juan DuJun Lu
Apr 28, 2011·CA: a Cancer Journal for Clinicians·Danijela Jelovac, Deborah K Armstrong
Jun 21, 2011·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal

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Citations

Nov 19, 2015·International Journal of Molecular Sciences·Mónica Martínez-FernándezJesús M Paramio
Apr 11, 2019·International Journal of Cancer. Journal International Du Cancer·Ielizaveta GorodetskaAnna Dubrovska
Nov 3, 2017·Gynecologic Oncology Research and Practice·Jill K Alldredge, Ramez N Eskander
Aug 2, 2018·Molecular Cancer·Qilian YangShengtao Zhou
Aug 19, 2021·Neurochemical Research·Pengfei GaoXianlong Zhang

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