HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

v-src activation of the collagenase-1 (matrix metalloproteinase-1) promoter through PEA3 and STAT: requirement of extracellular signal-regulated kinases and inhibition by retinoic acid receptors.

Abstract
Collagenase-1 (matrix metalloproteinase-1 (MMP-1)) degrades the extracellular matrix and enhances the invasive phenotype of tumor cells. v-src activated MMP-1 transcription through a series of elements in the proximal promoter, including the E2BP (nt -172), polyoma virus enhancer A3 (PEA3) (nt -94), activator protein-1 (AP-1) (nt -72), and signal transducer and activator of transcription (STAT) (nt -57) consensus sites. Of these sites, PEA3 and STAT contributed specifically to induction by v-src, whereas the remaining elements were also involved in induction by the phorbol ester phorbol myristate acetate (PMA). However, in contrast to MMP-1 induction by PMA, an AP-1 site located at nt -186 did not contribute to v-src induction. These results suggest divergence of the tyrosine kinase- and protein kinase C-dependent pathways with respect to MMP-1 transcription. v-src induced MMP-1 through mitogen-activated protein kinases, with extracellular signal-regulated kinases playing a larger role than c-jun N-terminal kinase. Retinoic acid, which inhibits the progression of certain cancers, repressed v-src-induced MMP-1 transcription. Constitutive expression of retinoic acid receptors (RARs) alpha or beta, but not gamma, or of retinoid X receptor alpha, repressed v-src-induced collagenase-1 transcription. We concluded that oncogenic induction of MMP-1 by v-src depends on signaling pathways and cis-acting sequences that are distinct from those involved in phorbol ester activation. Furthermore, v-src induction of MMP-1 may, by acting in concert with other genes, enhance matrix degradation and tumor progression, and retinoic acid and RARs may antagonize this induction in an RAR type-specific manner.
AuthorsM P Vincenti, D J Schroen, C I Coon, C E Brinckerhoff
JournalMolecular carcinogenesis (Mol Carcinog) Vol. 21 Issue 3 Pg. 194-204 (Mar 1998) ISSN: 0899-1987 [Print] United States
PMID9537651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • Receptors, Retinoic Acid
  • Trans-Activators
  • Transcription Factors
  • transcription factor PEA3
  • Tretinoin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Collagenases
  • Matrix Metalloproteinase 1
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases (physiology)
  • Collagenases (genetics, metabolism)
  • Consensus Sequence
  • Down-Regulation
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Genes, src
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase Inhibitors
  • Molecular Sequence Data
  • Promoter Regions, Genetic (physiology)
  • Rabbits
  • Receptors, Retinoic Acid (physiology)
  • Signal Transduction (drug effects, physiology)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Trans-Activators (physiology)
  • Transcription Factors (physiology)
  • Transcriptional Activation (drug effects, physiology)
  • Tretinoin (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: