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EVI1, a target gene for amplification at 3q26, antagonizes transforming growth factor-β-mediated growth inhibition in hepatocellular carcinoma.

Yasui K, Konishi C, Gen Y, Endo M, Dohi O, Tomie A, Kitaichi T, Yamada N, Iwai N, Nishikawa T, Yamaguchi K, Moriguchi M, Sumida Y, Mitsuyoshi H, Tanaka S, Arii S, Itoh Y - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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Map of the amplicon at 3q26 in the JHH-1 hepatocellular carcinoma (HCC) cell line. (a) Recurrent copy number gains on the chromosomal region 3q26 in HCC cell lines assessed using a GeneChip Mapping array. Copy number gains are indicated by red horizontal lines above the chromosome ideogram. A high-level gain (amplification) is indicated by the yellow rectangle. Copy number losses are indicated by green lines under the chromosome ideogram. Each horizontal line represents an aberration detected in a single HCC cell line. (b) Copy number profile of chromosome (Chr) 3 in JHH-1 cells. The position of the Affymetrix single nucleotide polymorphism (SNP) probes, the genes present, the bacterial artificial chromosomes (BACs) used as probes for FISH experiments, and the sequence-tagged site (STS) marker used for real-time quantitative PCR are shown based on the University of California Santa Cruz genome database. (c) Representative images of FISH analysis of metaphase chromosomes from JHH-1 cells using the following bacterial artificial chromosome probes: paired RP11-721P22 (containing EVI1; green) and RP11-137H17 (containing MDS1; red). The arrow indicates six signals each for red and green. Cen, centromere; Tel, telomere.
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fig01: Map of the amplicon at 3q26 in the JHH-1 hepatocellular carcinoma (HCC) cell line. (a) Recurrent copy number gains on the chromosomal region 3q26 in HCC cell lines assessed using a GeneChip Mapping array. Copy number gains are indicated by red horizontal lines above the chromosome ideogram. A high-level gain (amplification) is indicated by the yellow rectangle. Copy number losses are indicated by green lines under the chromosome ideogram. Each horizontal line represents an aberration detected in a single HCC cell line. (b) Copy number profile of chromosome (Chr) 3 in JHH-1 cells. The position of the Affymetrix single nucleotide polymorphism (SNP) probes, the genes present, the bacterial artificial chromosomes (BACs) used as probes for FISH experiments, and the sequence-tagged site (STS) marker used for real-time quantitative PCR are shown based on the University of California Santa Cruz genome database. (c) Representative images of FISH analysis of metaphase chromosomes from JHH-1 cells using the following bacterial artificial chromosome probes: paired RP11-721P22 (containing EVI1; green) and RP11-137H17 (containing MDS1; red). The arrow indicates six signals each for red and green. Cen, centromere; Tel, telomere.

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.


EVI1, a target gene for amplification at 3q26, antagonizes transforming growth factor-β-mediated growth inhibition in hepatocellular carcinoma.

Yasui K, Konishi C, Gen Y, Endo M, Dohi O, Tomie A, Kitaichi T, Yamada N, Iwai N, Nishikawa T, Yamaguchi K, Moriguchi M, Sumida Y, Mitsuyoshi H, Tanaka S, Arii S, Itoh Y - Cancer Sci. (2015)

Map of the amplicon at 3q26 in the JHH-1 hepatocellular carcinoma (HCC) cell line. (a) Recurrent copy number gains on the chromosomal region 3q26 in HCC cell lines assessed using a GeneChip Mapping array. Copy number gains are indicated by red horizontal lines above the chromosome ideogram. A high-level gain (amplification) is indicated by the yellow rectangle. Copy number losses are indicated by green lines under the chromosome ideogram. Each horizontal line represents an aberration detected in a single HCC cell line. (b) Copy number profile of chromosome (Chr) 3 in JHH-1 cells. The position of the Affymetrix single nucleotide polymorphism (SNP) probes, the genes present, the bacterial artificial chromosomes (BACs) used as probes for FISH experiments, and the sequence-tagged site (STS) marker used for real-time quantitative PCR are shown based on the University of California Santa Cruz genome database. (c) Representative images of FISH analysis of metaphase chromosomes from JHH-1 cells using the following bacterial artificial chromosome probes: paired RP11-721P22 (containing EVI1; green) and RP11-137H17 (containing MDS1; red). The arrow indicates six signals each for red and green. Cen, centromere; Tel, telomere.
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Related In: Results  -  Collection

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fig01: Map of the amplicon at 3q26 in the JHH-1 hepatocellular carcinoma (HCC) cell line. (a) Recurrent copy number gains on the chromosomal region 3q26 in HCC cell lines assessed using a GeneChip Mapping array. Copy number gains are indicated by red horizontal lines above the chromosome ideogram. A high-level gain (amplification) is indicated by the yellow rectangle. Copy number losses are indicated by green lines under the chromosome ideogram. Each horizontal line represents an aberration detected in a single HCC cell line. (b) Copy number profile of chromosome (Chr) 3 in JHH-1 cells. The position of the Affymetrix single nucleotide polymorphism (SNP) probes, the genes present, the bacterial artificial chromosomes (BACs) used as probes for FISH experiments, and the sequence-tagged site (STS) marker used for real-time quantitative PCR are shown based on the University of California Santa Cruz genome database. (c) Representative images of FISH analysis of metaphase chromosomes from JHH-1 cells using the following bacterial artificial chromosome probes: paired RP11-721P22 (containing EVI1; green) and RP11-137H17 (containing MDS1; red). The arrow indicates six signals each for red and green. Cen, centromere; Tel, telomere.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Show MeSH
Related in: MedlinePlus