Channelpedia

PubMed 23580589


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC3



Title: FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3.

Authors: Xiang Tao, Naiqing Zhao, Hongyan Jin, Zhenbo Zhang, Yintao Liu, Jian Wu, Robert C Bast, Yinhua Yu, Youji Feng

Journal, date & volume: Endocr. Relat. Cancer, 2013 Jun , 20, 415-29

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23580589


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.