Lin Sheng1, Dong-yuan Liu, Keng Shen. 1. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Abstract
OBJECTIVE: There is only a limited direct indication that gonadotropins play a role in the genesis and development of epithelial ovarian cancer (EOC). Follicle-stimulating hormone (FSH) can enhance the growth of epithelial ovarian cancer cell in vitro. The research is to investigate the pathway of FSH action in epithelial ovarian cancer cell. METHODS: Epithelial ovarian cancer cell line OVCAR3 was transfected with FSH receptor cDNA expressing vector. The transfected cells that are sensitive highly to FSH stimulation were got, and named OVCAR3-FSHR. Adding FSH to the cells, or treating the cells with protein kinase C (PKC) activator tetradenocanoyl phorbol acetate (TPA), PKC inhibitor tamoxifen (TAM) in meantime, methyl thiazolyl tetrazolium (MTT) method was used to study the proliferation of cells. RT-polymerase chain reaction was used to identity the mRNA expression of various PKC subtypes. Westernblot was for detection of protein expression of PKCalpha and phosphorylated PKCalpha. RESULTS: FSH can promote proliferation of OVCAR3-FSHR (1.9 folds). There is some increase in PKCalpha by the FSH stimulation. The phosphorylated PKCalpha expression were enhanced significantly too. Both the amount and activity of PKCalpha were increased in response to FSH. TPA and TAM suppress FSH-stimulated cell growth (60% and 47%). Meanwhile expression level of PKCalpha was decreased with the co-treatment of TPA or TAM and FSH comparing with treatment with FSH only. CONCLUSIONS: FSH promoted epithelial ovarian cancer cell proliferation through PKC pathway. It plays a role in the development of epithelial ovarian cancer.
OBJECTIVE: There is only a limited direct indication that gonadotropins play a role in the genesis and development of epithelial ovarian cancer (EOC). Follicle-stimulating hormone (FSH) can enhance the growth of epithelial ovarian cancer cell in vitro. The research is to investigate the pathway of FSH action in epithelial ovarian cancer cell. METHODS:Epithelial ovarian cancer cell line OVCAR3 was transfected with FSH receptor cDNA expressing vector. The transfected cells that are sensitive highly to FSH stimulation were got, and named OVCAR3-FSHR. Adding FSH to the cells, or treating the cells with protein kinase C (PKC) activator tetradenocanoyl phorbol acetate (TPA), PKC inhibitor tamoxifen (TAM) in meantime, methyl thiazolyl tetrazolium (MTT) method was used to study the proliferation of cells. RT-polymerase chain reaction was used to identity the mRNA expression of various PKC subtypes. Westernblot was for detection of protein expression of PKCalpha and phosphorylated PKCalpha. RESULTS: FSH can promote proliferation of OVCAR3-FSHR (1.9 folds). There is some increase in PKCalpha by the FSH stimulation. The phosphorylated PKCalpha expression were enhanced significantly too. Both the amount and activity of PKCalpha were increased in response to FSH. TPA and TAM suppress FSH-stimulated cell growth (60% and 47%). Meanwhile expression level of PKCalpha was decreased with the co-treatment of TPA or TAM and FSH comparing with treatment with FSH only. CONCLUSIONS: FSH promoted epithelial ovarian cancer cell proliferation through PKC pathway. It plays a role in the development of epithelial ovarian cancer.