Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins
| Autor: | Kunihiro Okamura, Zongjuan Fang, Serdar E. Bulun, Mitsutoshi Tamura, Sijun Yang, Siby Sebastian, Bilgin Gurates |
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| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Stromal cell Response element Restriction Mapping Biology Transfection Endocrinology Enhancer binding Tumor Cells Cultured Humans Molecular Biology Sequence Deletion Ccaat-enhancer-binding proteins Base Sequence Reverse Transcriptase Polymerase Chain Reaction Membrane Proteins Promoter Molecular biology Endometrial Neoplasms Isoenzymes Cyclooxygenase 2 Mutagenesis Prostaglandin-Endoperoxide Synthases Culture Media Conditioned Enzyme Induction CCAAT-Enhancer-Binding Proteins Female biological phenomena cell phenomena and immunity Signal transduction Mitogen-Activated Protein Kinases Stromal Cells Oligonucleotide Probes |
| Zdroj: | Journal of molecular endocrinology. 31(1) |
| ISSN: | 0952-5041 |
| Popis: | We previously reported that human malignant endometrial epithelial cell conditioned medium (MECM) up-regulated cyclooxygenase (COX)-2 mRNA and protein levels in human normal endometrial stromal cells (ESC). Here we showed that pretreatment with a selective inhibitor of the extracellularly regulated kinase (ERK)1/2 signaling pathway blocked the MECM-induced COX-2 expression in ESC. Transient transfection assays indicated critical roles of a cAMP response element (CRE,-59/-53 bp) and a nuclear factor for interleukin (IL)-6 expression (NF-IL6) site (-132/-124 bp) in the regulation of basal and MECM-induced activity of COX-2 gene promoter in ESC. Employing electrophoretic mobility shift assays, we demonstrated that increased functional binding of CCAAT/enhancer binding protein (C/EBP)alpha, C/EBPbeta and upstream stimulatory factor-2 to the CRE and C/EBPalpha and C/EBPbeta to the NF-IL6 site were, at least in part, responsible for MECM-induced COX-2 expression in ESC. Moreover, overexpression of C/EBPalpha and C/EBPbeta significantly induced COX-2 promoter activity in ESC. Collectively, these results suggest that the basal and MECM-induced transcription of the COX-2 gene in ESC is regulated through a combination of the CRE and the NF-IL6 site by functional interactions of C/EBPalpha and C/EBPbeta. |
| Databáze: | OpenAIRE |
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