Role of CRE-Binding Protein (CREB) in Aromatase Expression in Breast Adipose View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-06

AUTHORS

Mariam Sofi, Morag J. Young, Theodora Papamakarios, Evan R. Simpson, Colin D. Clyne

ABSTRACT

Estrogen biosynthesis from C19 steroids is catalyzed by aromatase cytochrome P450. Aromatase is expressed in breast adipose tissue through the use of a distal, cytokine-responsive promoter (promoter I.4). Breast tumors, however, secrete soluble factors that over-stimulate aromatase expression through an alternative proximal cAMP-responsive promoter, promoter II. We have mapped the cAMP-responsive regions of promoter II by transient transfection of 3T3-L1 preadipocytes with aromatase promoter II reporter genes. 5' deletion and mutation analyses identified two cAMP response element (CRE)-like sequences (CRE1 and CRE2) that were essential for cAMP-induced promoter II activity. Electrophoretic mobility shift analysis demonstrated that CRE binding protein (CREB) bound to each element, and that this interaction was enhanced in the presence of cAMP. Quantification of CREB mRNA expression in adipose tissue from normal and tumor bearing breast adipose tissue revealed that CREB expression is approximately five times higher in tumor bearing than in normal breast adipose tissue. Thus, the over expression of aromatase in adipose tissue surrounding breast tumors could arise through increases in both CREB expression and CREB transcriptional activity. Pharmacological inhibition of CREB activity, previously shown to have anti-proliferative effects on cancer cells, might therefore have additional benefits through inhibition of aromatase expression and thus estrogen production in breast adipose. More... »

PAGES

399-407

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1024038632570

DOI

http://dx.doi.org/10.1023/a:1024038632570

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050838658

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12846424


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