Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 119; no. 1; pp. 14 - 25
• Main Authors: Ramayya, M.S., Sheng, M., Moroz, K., Hill, S.M., Rowan, B.G.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-03-2010; Elsevier
• Subjects: Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Biological and medical sciences; Cell Proliferation; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme - genetics; Cholesterol Side-Chain Cleavage Enzyme - metabolism; Disease Progression; Estrogen receptor; Female; Female genital diseases; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Models, Biological; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Ovarian epithelial cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovary - metabolism; Ovary - pathology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Progesterone; Progesterone - biosynthesis; Progesterone Reductase - genetics; Progesterone Reductase - metabolism; Steroidogenic Factor 1 - physiology; Steroidogenic factor-1; Tumors; Vertebrates: endocrinology; Vertebrates: reproduction; OSE; SFRE; Cell proliferation; Estrogen receptor; ERα; Ovarian epithelial cancer; FACS; PARP-1; Steroidogenic factor-1; StAR; IOSE; Progesterone; hSF-1; Apoptosis; Human; Ovary carcinoma; Growth; Biosynthesis; Malignant tumor; Cell surface; Ovarian hormone; Female genital diseases; Progestagen; Ovarian diseases; Cell death; Steroidogenesis; Sex steroid hormone; Cancer
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2009.11.006

The majority of cancers derived from ovarian surface epithelial (OSE) cells are lethal. Estrogens promote proliferation of OSE cells, whereas progesterone inhibits proliferation and promotes apoptosis of OSE cells. Human steroidogenic factor-1 (hSF-1) induction of the steroidogenic acute regulatory protein (
StAR) gene, and the steroidogenic enzymes CYP11A1 and HSD3B2 is central to progesterone biosynthesis. Whereas hSF-1 and StAR are expressed in human ovarian surface epithelial (HOSE) cells, hSF-1 and StAR protein were not expressed in a panel of malignant ovarian cancer cell lines (SKOV-3, BG-1, and Caov-3), and in human OSE cells immortalized by SV40 large T antigen (IOSE-121). Transient expression of hSF-1 in SKOV-3 cells activated the expression of StAR, p450scc and 3βHSD-II mRNAs, and induced progesterone biosynthesis. Additionally, hSF-1 suppressed proliferation and promoted apoptosis of SKOV-3 cells and suppressed SKOV-3 cell growth induced by ERα and estradiol. These findings suggest that hSF-1 is central to progesterone biosynthesis in OSE cells. Human SF-1 may decrease OSE cancer cell numbers directly by apoptosis, and indirectly by opposing estradiol-induced proliferation. These findings are consistent with the hypothesis, that down-regulation of hSF-1 contributes to progression of ovarian epithelial cancers.