Cyclic Adenosine 3′,5′-Monophosphate Response Element-Binding Protein and CCAAT/Enhancer-Binding Protein Mediate Prostaglandin E2-Induced Steroidogenic Acute Regulatory Protein Expression in Endometriotic Stromal Cells

Hsu CC, Chih-Chao Hsu, Lu CW, Chun Wun Lu, Chun-Wun Lu, Bu Miin Huang, Bu-Miin Huang, Huang BM, Meng-Hsing Wu, Wu MH, Shaw-Jenq Tsai, Shaw‐Jenq Tsai
The American Journal of Pathology · 2008 · vol. 173(2) , pp. 433–441 · doi:10.2353/ajpath.2008.080199 · PMID:18583320 · PMC2475780 · W1976913846
article OA: bronze CC0 ⤵ 21 in-corpus citations
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Prostaglandin E2 upregulates steroidogenic acute regulatory protein in endometriotic stromal cells by activating CREB and C/EBP transcription factors.

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Abstract

Aberrant expression of the steroidogenic acute regulatory (StAR) protein in human endometriotic stromal cells plays an important role in the development of endometriosis. Prostaglandin E(2) (PGE(2)) is a potent inducer of StAR expression in these cells; however, the mechanisms responsible for the transcriptional regulation of StAR remain to be elucidated. Herein we report that PGE(2)-induced StAR expression is independent of the transcriptional suppressor DAX-1 but is regulated by the transcriptional activator cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB). A promoter activity assay revealed that the cis-element needed for the binding of the CCAAT/enhancer-binding protein (C/EBP) was critical for PGE(2)-induced StAR expression. Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. Results from a chromatin immunoprecipitation assay demonstrated that the binding of C/EBPbeta to the StAR promoter was increased whereas CREB binding was unchanged after PGE(2) treatment. Taken together, PGE(2)-induced StAR promoter activity appears to be regulated by CREB and C/EBPbeta in a cooperative manner in ectopic human endometriotic stromal cells, providing a molecular framework for the etiology of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

CCAAT-Enhancer-Binding Proteins Cyclic AMP Response Element-Binding Protein Dinoprostone Endometriosis Phosphoproteins Binding Sites CCAAT-Enhancer-Binding Proteins Cells, Cultured Cyclic AMP Response Element-Binding Protein DAX-1 Orphan Nuclear Receptor Dinoprostone DNA-Binding Proteins DNA-Binding Proteins Endometriosis Endometriosis Female Gene Expression Regulation Humans Phosphoproteins Phosphoproteins

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