Dataset Information

Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.

ABSTRACT:

Background & aims

Myc is involved in cell growth, proliferation, apoptosis, energy metabolism, and differentiation. Whether it is essential for hepatocellular proliferation and carcinogenesis is unclear due to a lack of an efficient hepatocyte-specific Myc disruption model. This study used a novel genetic model to investigate the involvement of Myc in hepatocellular proliferation and hepatocarcinogenesis in mice.

Methods

Temporal hepatocyte-specific Myc disruption was achieved by use of the tamoxifen-inducible Cre-ER(T2) recombinase system under control of the serum albumin promoter. Hepatocyte proliferation was assessed by administering peroxisome proliferator-activated receptor α (PPARα) agonist Wy-14,643. A diethylnitrosamine-induced liver cancer model was used to evaluate the role of Myc in hepatocarcinogenesis.

Results

Tamoxifen administration induced recombination of Myc specifically in hepatocytes of Myc(fl/fl,ERT2-Cre) mice. When treated with a known hepatocellular proliferative stimulus Wy-14,643, Myc(fl/fl,ERT2-Cre) mice showed a lower liver/body weight ratio and suppressed hepatocyte proliferation as compared to Myc(fl/fl) mice. Hepatic expression of cell cycle control genes, DNA repair genes, and Myc target gene miRNAs were upregulated in Wy-14,643-treated Myc(fl/fl) mouse livers, but not in Wy-14,643-treated Myc(fl/fl,ERT2-Cre) livers. However, no differences were observed in the lipid-lowering effect of Wy-14,643 between Myc(fl/fl,ERT2-Cre) and Myc(fl/fl) mice, consistent with no differences in the expression of several PPARα target genes involved in fatty acid β-oxidation. Moreover, when subjected to the diethylnitrosamine liver cancer bioassay, Myc(fl/fl,ERT2-Cre) mice exhibited a markedly lower incidence of tumor formation compared with Myc(fl/fl) mice.

Conclusions

Myc plays an essential role in hepatocellular proliferation and liver tumorigenesis.

SUBMITTER: Qu A

PROVIDER: S-EPMC3909877 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.

Qu Aijuan A Jiang Changtao C Cai Yan Y Kim Jung-Hwan JH Tanaka Naoki N Ward Jerrold M JM Shah Yatrik M YM Gonzalez Frank J FJ

Journal of hepatology 20131002 2

<h4>Background & aims</h4>Myc is involved in cell growth, proliferation, apoptosis, energy metabolism, and differentiation. Whether it is essential for hepatocellular proliferation and carcinogenesis is unclear due to a lack of an efficient hepatocyte-specific Myc disruption model. This study used a novel genetic model to investigate the involvement of Myc in hepatocellular proliferation and hepatocarcinogenesis in mice.<h4>Methods</h4>Temporal hepatocyte-specific Myc disruption was achieved by ...[more]

PMID: 24096051

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Dataset Information

Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.

Background & aims

Methods

Results

Conclusions

Publications

Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.

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