Document Detail


Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells.
MedLine Citation:
PMID:  20045459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M S Ramayya; M Sheng; K Moroz; S M Hill; B G Rowan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-04
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  119     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-24     Completed Date:  2010-03-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  14-25     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Section of Pediatric Endocrinology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA. mramayya@tulane.edu
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics,  physiology
Cell Proliferation*
Cells, Cultured
Cholesterol Side-Chain Cleavage Enzyme / genetics,  metabolism
Disease Progression
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Models, Biological
Neoplasms, Glandular and Epithelial / genetics,  metabolism,  pathology*
Ovarian Neoplasms / genetics,  metabolism,  pathology*
Ovary / metabolism,  pathology
Phosphoproteins / genetics,  metabolism
Progesterone / biosynthesis*
Progesterone Reductase / genetics,  metabolism
Steroidogenic Factor 1 / physiology*
Chemical
Reg. No./Substance:
0/NR5A1 protein, human; 0/Phosphoproteins; 0/Steroidogenic Factor 1; 0/steroidogenic acute regulatory protein; 57-83-0/Progesterone; EC 1.1.1.145/3 beta-hydroxysteroid dehydrogenase type II; EC 1.1.1.145/Progesterone Reductase; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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