EVI1, a target gene for amplification at 3q26, antagonizes transforming growth factor-Î²-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: To determine whether the amplification of EVI1 that was observed in JHH-1 cells was relevant to primary human carcinomas, the copy number of EVI1 in primary HCC tumors was determined by quantitative PCR using a method similar to that used for the cell lines. A copy number gain of EVI1 was observed in 24 (36%) of the 66 tumors (Fig.3a).
Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.