Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis

Shunsuke Okuyama; Hiroyuki Marusawa; Tomonori Matsumoto; Yoshihide Ueda; Yuko Matsumoto; Yoko Endo; Atsushi Takai; Tsutomu Chiba

doi:10.1002/ijc.26114

journal article May 30, 2011

Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis

Shunsuke Okuyama Hiroyuki Marusawa Tomonori Matsumoto Yoshihide Ueda

Yuko Matsumoto Yoko Endo Atsushi Takai

Tsutomu Chiba

International Journal of Cancer Vol. 130 No. 6 pp. 1294-1301 · Wiley

View at Publisher Save 10.1002/ijc.26114

Abstract

AbstractApolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) was originally identified as a member of the cytidine deaminase family with putative nucleotide editing activity. To clarify the physiologic and pathologic roles, and the target nucleotide of APOBEC2, we established an APOBEC2 transgenic mouse model and investigated whether APOBEC2 expression causes nucleotide alterations in host DNA or RNA sequences. Sequence analyses revealed that constitutive expression of APOBEC2 in the liver resulted in significantly high frequencies of nucleotide alterations in the transcripts of eukaryotic translation initiation factor 4 gamma 2 (Eif4g2) and phosphatase and tensin homolog (PTEN) genes. Hepatocellular carcinoma developed in 2 of 20 APOBEC2 transgenic mice at 72 weeks of age. In addition, constitutive APOBEC2 expression caused lung tumors in 7 of 20 transgenic mice analyzed. Together with the fact that the proinflammatory cytokine tumor necrosis factor‐α induces ectopic expression of APOBEC2 in hepatocytes, our findings indicate that aberrant APOBEC2 expression causes nucleotide alterations in the transcripts of the specific target gene and could be involved in the development of human hepatocellular carcinoma through hepatic inflammation.

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Details

Published: May 30, 2011
Vol/Issue: 130(6)
Pages: 1294-1301
License: View

Authors

Department of Gastroenterology and Hepatology Graduate School of Medicine Kyoto University Kyoto Japan

T

Tsutomu Chiba

Cite This Article

Shunsuke Okuyama, Hiroyuki Marusawa, Tomonori Matsumoto, et al. (2011). Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis. International Journal of Cancer, 130(6), 1294-1301. https://doi.org/10.1002/ijc.26114

Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis

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