High mobility group protein HMGI(Y) enhances tumor cell growth, invasion, and matrix metalloproteinase‐2 expression in prostate cancer cells

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Abstract
BACKGROUND The high mobility group protein HMGI(Y) has oncogenic properties and correlates with an aggressive phenotype in prostate cancer. The molecular mechanisms involved in transformation associated with HMGI(Y) overexpression remain unknown. METHODS The HMG-I isoform was transfected and overexpressed in nonmetastatic Dunning prostate cancer cells (G cells) without detectable HMGI(Y). The assays of cell proliferation, tumor formation, in vitro invasion, and cDNA microarray were performed to assess the effect of HMGI(Y) overexpression in the transfected G cells. RESULTS Overexpression of HMG-I in G cells significantly increases cell proliferation and tumor growth and also modestly enhances in vitro invasion compared to mock transfectant. cDNA microarray revealed that expression of the matrix metalloproteinase-2 (MMP-2) proform was increased eightfold in G cells overexpressing HMG-I. CONCLUSIONS Overexpression of HMG-I in prostate cancer cells enhances cell growth, invasion, and expression of the proform of MMP-2, which may initiate early steps involved in the metastatic cascade.