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Evidence that estrogen receptor beta enhances MMP-13 promoter activity in HIG-82 cells and that this enhancement can be influenced by ligands and involves specific promoter sites

Evidence that estrogen receptor beta enhances MMP-13 promoter activity in HIG-82 cells and that this enhancement can be influenced by ligands and involves specific promoter sites

Biochemistry and Cell Biology 85(3): 326-336

ISSN/ISBN: 0829-8211

PMID: 17612627

DOI: 10.1139/o07-016

Degradation of articular cartilage is characteristic of osteoarthritis, and matrix metal loprotei nase-13 (MMP- 13) has been implicated in this condition. Estrogen receptors (ERs) are present in connective tissues, indicating these tissues' potential responsiveness to estrogen. We based this study on the hypothesis that estrogen receptor P (ERP) can modulate MMP-13 promoter activity. Transfection of cells with ER beta constructs led to the induction of the endogenous MMP-13 Gene, as evidenced by increased mRNA levels. The results also indicated that MMP-13 promoter construct activity in the HIG-82 cell line significantly increased when ER beta was present, and that estrogen downregulated this response in a dose-dependent manner. ER beta was shown to enhance MMP-13 expression somewhat more strongly than ER alpha, and the impact of a number of selective ER modulators (tamoxifen, raloxifene, and ICI 182,780) on ER beta enhancement of promoter activity was found to be significantly less than that of estrogen. Furthermore, transcription regulatory sites in the MMP-13 promoter, specifically AP-1 and PEA-3, were shown to act in conjunction to mediate ER beta effects. Thus, ER beta likely influences MMP-13 promoter expression in normal and disease processes.

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Accession: 015759875

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