SWITCH FROM MONOALLELIC TO BIALLELIC HUMAN IGF2 PROMOTER METHYLATION DURING AGING AND CARCINOGENESIS

Citation
Jpj. Issa et al., SWITCH FROM MONOALLELIC TO BIALLELIC HUMAN IGF2 PROMOTER METHYLATION DURING AGING AND CARCINOGENESIS, Proceedings of the National Academy of Sciences of the United Statesof America, 93(21), 1996, pp. 11757-11762
Citations number
37
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
93
Issue
21
Year of publication
1996
Pages
11757 - 11762
Database
ISI
SICI code
0027-8424(1996)93:21<11757:SFMTBH>2.0.ZU;2-4
Abstract
We have previously linked aging, carcinogenesis, and de novo methylati on within the promoter of the estrogen receptor (ER) gene in human col on. We now examine the dynamics of this process for the imprinted gene for insulin-like growth factor II (IGF2). In young individuals, the P 2-4 promoters of IGF2 are methylated exclusively on the silenced mater nal allele. During aging, this promoter methylation becomes more exten sive and involves the originally unmethylated allele. Most adult human tumors, including colon, breast, lung, and leukemias, exhibit increas ed methylation at the P2-4 IGF2 promoters, suggesting further spreadin g during the neoplastic process. In tumors, this methylation is associ ated with diminished or absent IGF2 expression from the methylated P3 promoter but maintained expression from P1, an upstream promoter that is not contained within the IGF2 CpG island. Our results demonstrate a remarkable evolution of methylation patterns in the imprinted promote r of the IGF2 gene during aging and carcinogenesis, and provide furthe r evidence for a potential link between aberrant methylation and disea ses of aging.