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

摘要

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