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

T Brabletz; A Jung; S Dag; F Hlubek; T Kirchner

doi:10.1016/s0002-9440(10)65204-2

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.

Authors

T Brabletz¹, A Jung, S Dag, F Hlubek, T Kirchner

Affiliation

¹ Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany. thomas.brabletz@patho.med.uni-erlangen.de

Abstract

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

Substances

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