title: 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.
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.
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Hsu
authors.forename: Chun-Wun
authors.initials: CW
authors.lastname: Lu
authors.forename: Bu-Miin
authors.initials: BM
authors.lastname: Huang
authors.forename: Meng-Hsing
authors.initials: MH
authors.lastname: Wu
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology*; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements; D017154:Stromal Cells / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D010750:Phosphoproteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000098682:Steroidogenic Acute Regulatory Protein; D015232:Dinoprostone