Follicle-stimulating hormone activates mitogen-activated protein kinase in preneoplastic and neoplastic ovarian surface epithelial cells

• Published in: The journal of clinical endocrinology and metabolism 2002-05, Vol.87 (5), p.2245-2253
• Main Authors: CHOI, Kyung-Chul, SUNG KEUN KANG, TAI, Chen-Jei, AUERSPERG, Nelly, LEUNG, Peter C. K
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; Cyclic AMP - metabolism; DNA-Binding Proteins; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Epithelial Cells - enzymology; Epithelial Cells - pathology; ets-Domain Protein Elk-1; Female; Female genital diseases; Flavonoids - pharmacology; Follicle Stimulating Hormone - pharmacology; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Hormone metabolism and regulation; Humans; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Mammalian male genital system; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Mitotic Index; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Phosphorylation - drug effects; Precancerous Conditions - enzymology; Precancerous Conditions - pathology; Proto-Oncogene Proteins - metabolism; Receptors, FSH - genetics; RNA, Messenger - metabolism; Transcription Factors; Tumors; Vertebrates: reproduction
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.87.5.2245

To investigate the role of FSH in ovarian cancer development, the present study examined the expression of FSH receptor (FSH-R) and the effect of FSH on proliferation of normal, preneoplastic, and neoplastic ovarian surface epithelium (OSE) cells. Recently, immortalized OSE (IOSE) cell lines, including IOSE-29 (preneoplastic) and IOSE-29EC (neoplastic), were used. Our results indicated that FSH-R mRNA was expressed and that FSH exerted a growth stimulatory effect in normal, preneoplastic, and neoplastic OSE cells. To investigate the mechanism of the growth stimulatory effect, the activation of MAPKs by FSH was examined in preneoplastic and neoplastic OSE cells. Treatment with FSH resulted in MAPK activation of IOSE-29 and IOSE-29EC cells, whereas the stimulatory effect of FSH on cellular proliferation and MAPK activation was completely abolished in the presence of PD98059, a MAPK kinase inhibitor, suggesting that the growth stimulatory effect of FSH is mediated through MAPK activation in these OSE cells. In a time-dependent study, FSH significantly increased MAPK activity at 5-10 min in IOSE-29 cells. The activated MAPK declined to the control level after 20 min in these cells. Similarly, treatment with FSH significantly induced MAPK activation after 5 min and sustained it for 60 min in IOSE-29EC cells. In addition, treatment with FSH resulted in substantial phosphorylation of Elk-1, confirming that FSH action is mediated via activation of MAPK. In conclusion, we have demonstrated that FSH-R was expressed, and FSH induced growth stimulation in normal, preneoplastic, and neoplastic OSE cells. Furthermore, treatment with FSH stimulated activation of the MAPK cascade and phosphorylated Elk-1 in neoplastic OSE cells. These results suggest that the MAPK cascade may be involved in cellular functions such as growth stimulation in response to FSH in preneoplastic and neoplastic OSE cells.