title: Reactive oxygen species regulate FSH-induced expression of vascular             endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian             cancer.
abstract: Follicle-stimulating hormone (FSH) and the FSH receptor contribute to tumor             angiogenesis and are acknowledged risk factors for ovarian epithelial cancer (OEC).             Accumulating evidence suggests that FSH can induce vascular endothelial growth             factor (VEGF) and hypoxia inducible factor 1α (HIF1α) expression. We previously             demonstrated that FSH induces reactive oxygen species (ROS) production and activates             Nrf2 signaling. This study was performed to investigate whether FSH induces VEGF             expression via a ROS-mediated Nrf2 signaling pathway. In the current study, OET             cells were treated with FSH; dichlorofluorescein staining was used to determine             ROS generation, western blotting was used to quantify Nrf2 expression and VEGF             expression was measured using an ELISA. Nrf2 and HIF1α were knocked down using             siRNAs to investigate the role of the Nrf2 and HIF1α signaling pathways in FSH-induced             VEGF expression. The chromatin immunoprecipitation assay (ChIP) was used to determine             HIF1α binding to the VEGF promoter. Finally, it was found that FSH induced ROS             production and activated Nrf2 signaling; elimination of ROS or knockdown of Nrf2             blocked FSH-induced VEGF expression. Knockdown of Nrf2 impaired HIF1α signaling             activation. Blockage of the FSH-ROS-Nrf2-HIF1α signaling pathway attenuated FSH-induced             binding of HIF1α to the VEGF promoter. Collectively, this study indicates that             ROS and aberrant expression of Nrf2 play an important role in FSH-induced angiogenesis             in OEC, and provides insight into the mechanisms of FSH-induced VEGF expression.             Elimination of ROS or inhibition of Nrf2 may represent potential therapeutic targets             for the treatment of ovarian cancer.
authors: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University, Affiliated First People's Hospital, Shanghai, PR China.
authors: Zhenbo
authors: Z
authors: Zhang
authors: Qianqian
authors: Q
authors: Wang
authors: Jie
authors: J
authors: Ma
authors: Xiaofang
authors: X
authors: Yi
authors: Yaping
authors: Y
authors: Zhu
authors: Xiaowei
authors: X
authors: Xi
authors: Youji
authors: Y
authors: Feng
authors: Zhijun
authors: Z
authors: Jin
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt