Document Detail


Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element.
MedLine Citation:
PMID:  15688015     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Estrogen is critical to both normal mammary gland and breast cancer development. Circulating levels of estrogen in premenopausal women are primarily determined by the action of aromatase in ovarian granulosa cells that converts testosterone to estradiol. In the current study, we unraveled an important role of Jun proteins in modulating ovary-specific aromatase expression. Ectopic expression of the Jun proteins in a human granulosa cell line significantly inhibited an ovary-specific promoter (PII) of the aromatase gene, whereas expression of dominant-negative mutants of Jun led to increased promoter activity. The Jun-mediated repression was specific to the aromatase promoter, as Jun proteins stimulated known AP1-responsive promoters in the same cellular context. Both the activation and basic leucine zipper domains of Jun were required for the transcriptional repression. Electrophoretic gel mobility assay showed that endogenous Jun proteins bound to a functionally important cAMP-responsive element (CRE) in the PII promoter-proximal region. Alteration of the CRE-like site impaired both the cAMP-responsive transcriptional activation and Jun-mediated repression. Furthermore, chromatin immunoprecipitation indicated the presence of cJun at the proximal region of the native PII promoter. Taken together, our work suggests that Jun proteins may attenuate estrogen biosynthesis by directly downregulating transcription of the aromatase gene in ovarian granulosa cells.
Authors:
Sagar Ghosh; Yimin Wu; Rong Li; Yanfen Hu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-24     Completed Date:  2005-04-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2236-46     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aromatase / genetics*
Cyclic AMP / physiology*
Female
Genes, jun
Granulosa Cells
Mice
Promoter Regions, Genetic*
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Transcriptional Activation
Grant Support
ID/Acronym/Agency:
CA093506/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-jun; 60-92-4/Cyclic AMP; EC 1.14.14.1/Aromatase

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


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