title: FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3.
abstract: Recent studies have suggested that FSH plays an important role in ovarian epithelial carcinogenesis. We demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis and facilitates neovascularisation. Our previous work has shown that transient receptor potential channel C3 (TRPC3) contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between FSH and TRPC3. We found that FSH stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. siRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and blocked apoptosis in ovarian cancer cell lines. FSH stimulation was associated with the up-regulation of TRPC3, while also facilitating the influx of Ca(2)(+) after treatment with a TRPC-specific agonist. Knockdown of TRPC3 abrogated FSH-stimulated Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1-α and VEGF. Ovarian cancer specimens were analysed for TRPC3 expression; higher TRPC3 expression levels correlated with early relapse and worse prognosis. Association with poor disease-free survival and overall survival remained after adjusting for clinical stage and grade. In conclusion, TRPC3 plays a significant role in the stimulating activity of FSH and could be a potential therapeutic target for the treatment of ovarian cancer, particularly in postmenopausal women with elevated FSH levels.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tao
authors.forename: Naiqing
authors.initials: N
authors.lastname: Zhao
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jin
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yintao
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Yu
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium
keywords: cell proliferation; follicle-stimulating hormone (FSH); ovarian epithelial cancer; prognosis; transient receptor potential channel C3 (TRPC3)