Imprinted genes in liver carcinogenesis

被引:91
作者
deSouza, AT
Yamada, T
Mills, JJ
Jirtle, RL
机构
[1] DUKE UNIV, MED CTR, DEPT RADIAT ONCOL, DURHAM, NC 27710 USA
[2] SUMITOMO CHEM CO LTD, ENVIRONM HLTH SCI LAB, OSAKA, JAPAN
[3] ZENECA PHARMACEUT, DEPT SAFETY MED, MACCLESFIELD SK10 4TG, CHESHIRE, ENGLAND
关键词
M6P/IGF2R; IGF2; genomic imprinting; tumor suppressor gene;
D O I
10.1096/fasebj.11.1.9034167
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Each cell contains both maternal and paternal copies of all genes except those that reside on the sex chromosomes, However, because of a phenomenon termed genomic imprinting, genes are biallelically expressed, Imprinted genes play an important role in embryogenesis and recently have also been shown to be mechanistically involved in carcinogenesis, The growing list of imprinted genes implicated in tumor formation includes both a growth factor gene, insulin-like growth factor 2 (IGF2), and a receptor gene, mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R). Elevated expression of IGF2 is often found in turners, and loss of imprinting is one mechanism by which its expression is deregulated, The M6P/IGF2R functions in the inactivation of the mitogen IGF2 and in the activation of the growth inhibitor, transforming growth factor beta, Recently, a high frequency of loss of heterozygosity with concomitant mutations in the remaining allele has been shown to occur at the M6P/IGF2R locus (i.e., 6q26-q27) in both human liver and breast tumors, suggesting that this gene functions as a tumor suppressor, Expression of the M6P/IGF2R gene is biallelic hi most humans but is monoallelic in mice, This species difference hi M6P/IGF2R gene imprinting provides one plausible explanation for the enhanced sensitivity of mice to tumor formation, Furthermore, these findings suggest that species differences in the imprinted status of genes mechanistically involved in tumor formation should be factored into human carcinogenesis risk assessment models when extrapolating results from mice to humans.
引用
收藏
页码:60 / 67
页数:8
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