beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer

Am J Pathol. 1999 Oct;155(4):1033-8. doi: 10.1016/s0002-9440(10)65204-2.


Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of beta-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Nucleus / metabolism
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • Gene Expression Regulation, Neoplastic
  • Genes, APC
  • Genes, Dominant
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Matrix Metalloproteinase 7 / genetics
  • Promoter Regions, Genetic / genetics
  • Recombinant Fusion Proteins / metabolism
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • beta Catenin


  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Recombinant Fusion Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • Glutathione Transferase
  • Matrix Metalloproteinase 7