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
| Autor: | Chih Chao Hsu, Bu Miin Huang, Chun Wun Lu, Shaw Jenq Tsai, Meng Hsing Wu |
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| Rok vydání: | 2008 |
| Předmět: |
endocrine system
medicine.medical_specialty Receptors Retinoic Acid Response element Endometriosis Repressor Biology Response Elements CREB Dinoprostone Pathology and Forensic Medicine Internal medicine medicine Humans Electrophoretic mobility shift assay Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Cells Cultured Regulation of gene expression Binding Sites Ccaat-enhancer-binding proteins DAX-1 Orphan Nuclear Receptor Binding protein Steroidogenic acute regulatory protein Phosphoproteins Cell biology DNA-Binding Proteins Repressor Proteins Endocrinology Gene Expression Regulation CCAAT-Enhancer-Binding Proteins biology.protein Female Stromal Cells Regular Articles |
| Zdroj: | The American Journal of Pathology. 173:433-441 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2008.080199 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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