EVI1, a target gene for amplification at 3q26, antagonizes transforming growth factor-β-mediated growth inhibition in hepatocellular carcinoma.
Bottom Line: Knockdown of EVI1 resulted in increased induction of the cyclin-dependent kinase inhibitor p15(INK) (4B) by transforming growth factor (TGF)-β and decreased expression of c-Myc, cyclin D1, and phosphorylated Rb in TGF-β-treated cells.Consequently, knockdown of EVI1 led to reduced DNA synthesis and cell viability.Collectively, our results suggest that EVI1 is a probable target gene that acts as a driving force for the amplification at 3q26 in HCC and that the oncoprotein EVI1 antagonizes TGF-β-mediated growth inhibition of HCC cells.
Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.Show MeSH
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Mentions: The DNA copy number of EVI1 was then determined in the 20 HCC cell lines by using quantitative PCR. The sequence-tagged site marker, SHGC-77524, which is specific for EVI1, was used for this PCR (Fig.1b). For this analysis, copy number changes were counted as gains if the copy number for a given tumor cell line exceeded the mean plus two standard deviations of that in normal lymphocytes. A copy number gain of EVI1 was observed in seven (35%) of the 20 cell lines (Fig.2a). As expected, JHH-1 cells showed the highest copy number gain.
Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.