Constitutive expression and regulation of collagenase-3 in human breast cancer cells

Mol Cell Biol Res Commun. 2000 Apr;3(4):218-23. doi: 10.1006/mcbr.2000.0215.

Abstract

Matrix metalloproteinases (MMPs) are a family of secreted or transmembrane proteins that have been implicated in multiple physiological and pathological processes related to extracellular matrix turnover. Recent evidence strongly suggests a role for collagenase-3 (MMP-13) in tumor metastasis and invasion. We report here that collagenase-3 is constitutively expressed in the breast cancer cell line MDA-MB231 (MDA) and outline the molecular mechanism regulating its expression. Functional analysis of the collagenase-3 promoter showed that both the activator protein-1 (AP-1) site and the runt domain (RD) binding site were required for maximal constitutive expression of collagenase-3 in MDA cells. Determination of factors binding to those sites by Northern analysis and transient transfections identified the requirement of Fra-1, c-Jun, and Cbfa1 for basal collagenase-3 promoter activity in MDA cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Collagenases / genetics*
  • Collagenases / metabolism
  • Core Binding Factor Alpha 1 Subunit
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Genes, jun / genetics
  • Humans
  • Matrix Metalloproteinase 13
  • Neoplasm Proteins*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RUNX1 Translocation Partner 1 Protein
  • Response Elements / genetics
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Core Binding Factor Alpha 1 Subunit
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1T1 protein, human
  • Transcription Factor AP-1
  • Transcription Factors
  • fos-related antigen 1
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13