Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis.

Abstract	To evaluate the significance of alterations in DNA methylation during human hepatocarcinogenesis, we examined levels of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and the DNA methylation status in 67 hepatocellular carcinomas (HCCs). The average level of mRNA for DNMT1 and DNMT3a was significantly higher in noncancerous liver tissues showing chronic hepatitis or cirrhosis than in histologically normal liver tissues, and was even higher in HCCs. Significant overexpression of DNMT3b and reduced expression of DNMT2 were observed in HCCs compared with the corresponding noncancerous liver tissues. DNA hypermethylation on CpG islands of the p16 (8% and 66%) and hMLH1 (0% and 0%) genes and methylated in tumor (MINT) 1 (6% and 34%), 2 (24% and 58%), 12 (21% and 33%), 25 (0% and 5%), and 31 (0% and 23%) clones, and DNA hypomethylation on satellites 2 and 3 (18% and 67%), were detected in noncancerous liver tissues and HCCs, respectively. There was no significant correlation between the expression level of any DNA methyltransferase and DNA methylation status. Reduced expression of DNA repair protein, MBD4, was significantly correlated with poorer tumor differentiation and involvement of portal vein. Slightly reduced expression of MBD2 was detected in HCCs, and the expression of MeCP2 was particularly reduced in HCCs with portal vein involvement. These data suggest that overexpression of DNMT1 and DNMT3a, DNA hypermethylation on CpG islands, and DNA hypomethylation on pericentromeric satellite regions are early events during hepatocarcinogenesis, and that reduced expression of MBD4 may play a role in malignant progression of HCC.
Authors	Y Saito, Y Kanai, M Sakamoto, H Saito, H Ishii, S Hirohashi
Journal	Hepatology (Baltimore, Md.) (Hepatology) Vol. 33 Issue 3 Pg. 561-8 (Mar 2001) ISSN: 0270-9139 [Print] United States
PMID	11230735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Chromosomal Proteins, Non-Histone DNA, Satellite DNA-Binding Proteins DNMT3A protein, human Dnmt3a protein, mouse MECP2 protein, human Methyl-CpG-Binding Protein 2 RNA, Messenger Repressor Proteins Dnmt2 protein, mouse DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases DNA Methyltransferase 3A DNMT1 protein, human Dnmt1 protein, mouse TRDMT1 protein, human
Topics	Adult Aged Carcinoma, Hepatocellular (genetics) Carrier Proteins (genetics) Centromere (genetics) Chromosomal Proteins, Non-Histone CpG Islands (genetics) DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases (genetics) DNA Methylation DNA Methyltransferase 3A DNA, Satellite (genetics) DNA-Binding Proteins (metabolism) Female Humans Liver Neoplasms (genetics) Male Methyl-CpG-Binding Protein 2 Middle Aged RNA, Messenger (metabolism) Repressor Proteins DNA Methyltransferase 3B

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!