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Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis.
- Source :
-
International journal of cancer [Int J Cancer] 2012 Mar 15; Vol. 130 (6), pp. 1294-301. Date of Electronic Publication: 2011 May 30. - Publication Year :
- 2012
-
Abstract
- Apolipoprotein 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.<br /> (Copyright © 2011 UICC.)
- Subjects :
- APOBEC Deaminases
Animals
Base Sequence
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Cell Transformation, Neoplastic genetics
Cytidine Deaminase genetics
Eukaryotic Initiation Factor-4G genetics
Eukaryotic Initiation Factor-4G metabolism
Hep G2 Cells
Hepatocytes metabolism
Hepatocytes pathology
Humans
Liver Neoplasms genetics
Liver Neoplasms metabolism
Lung Neoplasms genetics
Lung Neoplasms metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle Proteins genetics
Nucleotides genetics
Nucleotides metabolism
PTEN Phosphohydrolase genetics
PTEN Phosphohydrolase metabolism
RNA Editing
Sequence Analysis methods
Tumor Necrosis Factor-alpha metabolism
Carcinoma, Hepatocellular pathology
Cell Transformation, Neoplastic metabolism
Cytidine Deaminase metabolism
Liver Neoplasms pathology
Lung Neoplasms pathology
Muscle Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 130
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 21469143
- Full Text :
- https://doi.org/10.1002/ijc.26114