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Role of matrix metalloproteinase‐2 in ethanol‐induced invasion by breast cancer cells
Author(s) -
Luo Jia
Publication year - 2006
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04578.x
Subject(s) - matrix metalloproteinase , cancer research , metastasis , receptor tyrosine kinase , stromal cell , cancer cell , medicine , breast cancer , cancer , biology , kinase , microbiology and biotechnology
Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying cellular/molecular mechanisms remain unknown. Amplification of ErbB2, a receptor tyrosine kinase, is found in 20–30% of breast cancer patients. Ethanol preferably stimulates invasion by breast cancer cells over‐expressing ErbB2 in vitro . Over‐expression of ErbB2 is positively associated with elevated levels of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9. Ethanol at physiologically relevant concentrations activates MMP‐2 without altering its expression level in mammary epithelial cells over‐expressing ErbB2, but not in cells expressing low levels of ErbB2. The activation is dependent on c‐jun N‐terminal kinases (JNK) and reactive oxygen species. Selective inhibitors of MMP‐2 and anti‐oxidants significantly inhibit ethanol‐stimulated cell invasion. Similarly, knocking down MMP‐2 by small interference RNA induces a partial blockage on ethanol‐promoted cell invasion. Matrix metalloproteinase‐2 is predominantly expressed in stromal fibroblasts; ethanol also activates fibroblastic MMP‐2. The conditioned medium collected from ethanol‐exposed fibroblasts dramatically stimulates the invasion of breast cancer cells. The role of MMP‐2 in ethanol‐induced tumor promotion is discussed.