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(American Journal of Pathology. 1999;155:1033-1038.)
© 1999 American Society for Investigative Pathology

Short Communication

ß-Catenin Regulates the Expression of the Matrix Metalloproteinase-7 in Human Colorectal Cancer

Thomas Brabletz, Andreas Jung, Serpil Dag, Falk Hlubek and Thomas Kirchner

From the Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany

Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of ß-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 ß-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.




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