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: Twenty HCC cell lines were screened for DNA copy number aberrations using GeneChip Mapping 100K and 250K arrays. Gains at the chromosomal region 3q26 were frequently found in 11 (55%) of the 20 cell lines (Fig.1a). Of these cell lines, JHH-1 cells showed a high-level copy number gain that is indicative of gene amplification at 3q26 (Fig.1b). The estimated extent of the amplification in JHH-1 cells was approximately 1.0 Mb. This chromosomal region lies between the Affymetrix markers, SNP_A-1696905 and SNP_A-1677515, and includes only MECOM, which is an officially assigned, but rarely used, gene name (Fig.1b). MECOM consists of MDS1 and EVI1 genes.
Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.