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Altered transcriptional regulation of the insulin‐like growth factor 2 gene in human hepatocellular carcinoma
Author(s) -
Uchida Kosaku,
Kondo Masashi,
Takeda Shin,
Osada Hirotaka,
Takahashi Toshitada,
Nakao Akimasa,
Takahashi Takashi
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199704)18:4<193::aid-mc2>3.0.co;2-f
Subject(s) - biology , promoter , insulin like growth factor 2 , allele , genomic imprinting , carcinogenesis , imprinting (psychology) , transcription factor , gene expression , gene , regulation of gene expression , genetics , hepatocellular carcinoma , cancer research , dna methylation
The insulin‐like growth factor 2 (IGF2) gene is regulated in a complex manner, involving developmentally regulated use of four different promoters as well as transcriptional repression of the maternal allele due to genomic imprinting. It has been well documented that the liver is an exceptional organ in which overall transcription from the four IGF2 promoters is markedly imbalanced towards preferential paternal expression only in fetal life, this being relaxed during the postnatal period, resulting in biallelic expression thereafter. We previously reported a marked allelic‐expression imbalance in the overall transcription of IGF2 in hepatocellular carcinoma (HCC), leading to preferential expression nonrandomly from the paternal allele. The study presented here, using 18 HCC specimens taken directly from patients, showed that this molecular change often reflects promoter switching from the adult P1 promoter to the fetal P2, P3, and P4 promoters. Interestingly, however, we found that restoration of allele‐specific expression of the P1 promoter nonrandomly from the paternal allele was also frequent in HCC, suggesting retention of an imprint for paternal expression from the P1 promoter of IGF2 in adult normal liver and altered availability of its modifying factor or factors in HCC. Further studies of the molecular mechanisms involved in the fluctuation of promoter usage and genomic imprinting of IGF2 are warranted to gain an insight into the biology of the liver in terms of development and oncogenesis. Mol. Carcinog. 18:193–198, 1997. © 1997 Wiley‐Liss, Inc.