Sheng Lin, Liu Dong-yuan, Shen Keng
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhonghua Fu Chan Ke Za Zhi. 2003 Dec;38(12):752-5.
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.
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.
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.
FSH promoted epithelial ovarian cancer cell proliferation through PKC pathway. It plays a role in the development of epithelial ovarian cancer.
仅有有限的直接证据表明促性腺激素在上皮性卵巢癌(EOC)的发生和发展中起作用。促卵泡激素(FSH)可在体外增强上皮性卵巢癌细胞的生长。本研究旨在探讨FSH在上皮性卵巢癌细胞中的作用途径。
用FSH受体cDNA表达载体转染上皮性卵巢癌细胞系OVCAR3。获得对FSH刺激高度敏感的转染细胞,命名为OVCAR3-FSHR。向细胞中添加FSH,或同时用蛋白激酶C(PKC)激活剂十四酰佛波醇乙酸酯(TPA)、PKC抑制剂他莫昔芬(TAM)处理细胞,采用甲基噻唑基四氮唑(MTT)法研究细胞增殖情况。用逆转录聚合酶链反应鉴定各种PKC亚型的mRNA表达。用蛋白质免疫印迹法检测PKCalpha和磷酸化PKCalpha的蛋白表达。
FSH可促进OVCAR3-FSHR的增殖(1.9倍)。FSH刺激可使PKCalpha有所增加。磷酸化PKCalpha的表达也显著增强。PKCalpha的量和活性均因FSH而增加。TPA和TAM抑制FSH刺激的细胞生长(分别为60%和47%)。同时,与仅用FSH处理相比,TPA或TAM与FSH共同处理时PKCalpha的表达水平降低。
FSH通过PKC途径促进上皮性卵巢癌细胞增殖。它在上皮性卵巢癌的发展中起作用。