Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms involved in retinoic acid (RA)-mediated regulation of the collagenase gene in a rabbit synovial fibroblast cell line (HIG82) were investigated. When HIG82 cells are cotransfected with expression vectors containing cDNAs for retinoic acid receptor (RAR) alpha 1, beta 2, or gamma 1 and collagenase promoter-driven CAT reporter constructs, only RAR-gamma 1 represses basal CAT expression upon RA treatment, while RAR-alpha 1, beta 2, and gamma 1 all suppress phorbol-induced CAT expression. Thus, transcriptional regulation of collagenase by RA is mediated by RARs in an RAR-type specific manner. Using mutational and deletional analysis, we find that interaction between elements within 182 bp collagenase promoter plays an important role in this process. In addition, cotreatment with RA results in a decrease of phorbol-induced mRNA levels of fos and jun, and binding of nuclear proteins to an AP-1 oligonucleotide. Furthermore, RA-induced nuclear protein(s) specifically bind to a 22 bp sequence (-182 to -161) of the collagenase promoter. We propose that RA-mediated regulation of the collagenase gene depends on the availability and interaction of specific RARs with multiple DNA elements within the promoter and with transcription factors, including AP-1 related proteins.
 ...
PMID:Differential regulation of collagenase gene expression by retinoic acid receptors--alpha, beta and gamma. 132 Feb 54

Retinyl methyl ether (RME) is known to prevent the development of mammary cancer. However, the mechanism by which RME exerts its anticancer effect is presently unclear. The diverse biological functions of retinoids, the vitamin A derivatives, are mainly mediated by their nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs are ligand-dependent transcriptional factors that either activate gene transcription through their binding to retinoic acid response elements or repress transactivation of genes containing the activator protein 1 (AP-1) binding site. Previous studies demonstrated that RME can modulate transcriptional activity of retinoid receptors on retinoic acid response elements, suggesting that regulation of retinoid receptor activity may mediate the anticancer effect of RME. In this study, we present evidence that RME can down-regulate AP-1 activity induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, insulin, growth factors, and the nuclear proto-oncogenes c-Jun and c-Fos. Transient transfection assays demonstrate that inhibition of AP-1 activity occurs on the human collagenase promoter containing an AP-1 binding site or the thymidine kinase promoter linked with an AP-1 binding site. In HeLa cells, the inhibition is observed when RAR-alpha and/or RXR-alpha but not RAR-beta or RAR-gamma expression vectors are cotransfected, whereas the endogenous retinoid receptors in breast cancer cells T-47D and ZR-75-1 were sufficient to confer the inhibition by RME. Furthermore, using gel retardation assay, we show that 12-O-tetradecanoylphorbol-13-acetate- and epidermal growth factor-induced AP-1 binding activity in breast cancer cells is inhibited by RME. These results suggest that one of the mechanisms by which RME prevents cancer development may be due to the repression of AP-1-responsive genes.
 ...
PMID:Retinyl methyl ether down-regulates activator protein 1 transcriptional activation in breast cancer cells. 927 11