Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site.

摘要: Stromelysin is a member of the metalloproteinase family which plays an important role in extracellular matrix remodelling during many normal and disease processes. We show here that polyomavirus-transformed rat embryo fibroblast cells (PyT21), transcription from stromelysin gene repressed by vitamin A derivative retinoic acid (RA). Furthermore, expression vectors encoding human RA receptors hRAR-alpha, hRAR-beta hRAR-gamma repress chloramphenicol acetyltransferase (CAT) promoter-CAT RA-treated PyT21 HeLa cells, as determined transient transfection assays. Through mutation deletion analysis, we dependent repression mediated 25 bp region nucleotide positions -72 to -48 5'-flanking DNA sequence. Further analysis this indicates sequence required for colocalizes with AP1 binding site essential promoter activity. also represses transcriptional activity reporter containing TPA responding driving HSV tk promoter. Thus RAR-RA complex appears blocking activation positive regulatory factors. However, found no evidence supporting possibility could be due RAR or components c-fos c-jun.