Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells.
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 3betaHSD-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 ERalpha 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.
Ramayya
M S
MS
Section of Pediatric Endocrinology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA. mramayya@tulane.edu
Sheng
M
M
Moroz
K
K
Hill
S M
SM
Rowan
B G
BG
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000502:physiology*; D000098682:Steroidogenic Acute Regulatory Protein
C515057:NR5A1 protein, human; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme