Follicle-stimulating hormone promotes the growth of human epithelial ovarian cancer cells through the protein kinase C-mediated system
2001
We have previously described that follicle-stimulating hormone (FSH) stimulated the growth of human epithelial ovarian cancer tissues and cells. In order to determine the signaling pathway on FSH action in ovarian cancer, we used an epithelial ovarian cancer cell line (HRA line) which constitutively FSH receptors (FSHRs). FSH significantly increased cell proliferation (230.1±20.5%, P<0.05) and 3H-thymidine uptake (443.5±35.1%, P<0.01). 1-(5-Isoquinolinesulfonyl)-2-methyipiperazine (H7, 1 5 nM), staurosponine (STR, 5 nM) and calphostin C (5 nM), specific protein kinase C (PKC) inhibitors, significantly suppressed the FSH-stimulated cell growth (120.2–140.2%, P<0.05) and 3H-thymidine uptake (140.5–173.9%, P<0.05), whereas N-(2-guanidinoethyl)-5-isoquinoline-sulfon-amide (HA1004, l5 nM), which is a derivant of H7 and inhibits most of protein kinases except PKC, showed no effect on the FSH-stimulated cell growth and 3H-thymidine uptake. A pretreatment with 12-0-tetradecanoylphorbol-13 acetate (TPA, 100 ng/ml) or STR (20 nM) significantly suppressed the subsequent FSH-stimulated cell growth (TPA; 152.3±10.3%, STR; 160.4±15.9%, P<0.05) and 3H-thymidine uptake (TPA; 250.4±18.3%, STR; 208.7±15.9%, P<0.05). STR abolished the suppression of TPA preincubation on the subsequent FSH-stimulated cell growth and 3H-thymidine uptake. HRA cells constitutively expressed PKCα but not PKCβ nor PKCγ. The levels of either expression of PKCα protein and mRNA were significantly amplified by FSH. These data suggest that stimulation of PKCα transcription is involved in the FSH-stimulated cell growth and DNA synthesis in epithelial ovarian cancer cells.
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