DNA methyltransferases 3a and 3b are differentially expressed in the early stages of a rat liver carcinogenesis model

Carcinogenesis is driven by the accumulation of mutations and abnormal DNA methylation patterns, particularly the hypermethylation of tumor-suppressor genes. Changes in genomic DNA methylation patterns are established by the DNA methyltransferases (DNMTs) family: DNMT1, DNMT3a and DNMT3b. The DNMTs...

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Published in:	Oncology reports Vol. 32; no. 5; pp. 2093 - 2103
Main Authors:	ANTÚNEZ, CARLOS ALBERTO VALENCIA, CHAYEB, LUCÍA TAJA, RODRÍGUEZ-SEGURA, MIGUEL ÁNGEL, ÁLVAREZ, GUADALUPE SOLEDAD LÓPEZ, GARCÍA-CUÉLLAR, CLAUDIA M, TREVIÑO, SAÚL VILLA
Format:	Journal Article
Language:	English
Published:	Greece D.A. Spandidos 01-11-2014 Spandidos Publications Spandidos Publications UK Ltd
Subjects:	2-Acetylaminofluorene Animals Cancer Carcinogenesis Cell cycle Cell growth Cyclin-Dependent Kinase Inhibitor p16 - genetics Deoxyribonucleic acid Diethylnitrosamine DNA DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - metabolism DNA Methylation DNA Methyltransferase 3A DNA Methyltransferase 3B DNA methyltransferases Enzymes Epigenetics expression profile Gene expression Gene Expression Regulation, Neoplastic hepatocellular carcinoma initiation Kinases Liver cancer Liver Neoplasms, Experimental - chemically induced Liver Neoplasms, Experimental - enzymology Liver Neoplasms, Experimental - pathology Male Methyltransferases Mutation Oncology, Experimental Oxidative stress Phase transitions Physiological aspects preneoplastic lesions progression promotion Proteins Rats resistant hepatocyte model Rodents Tissue Inhibitor of Metalloproteinase-3 - genetics Tumor Suppressor Proteins - genetics Tumors
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Summary:	Carcinogenesis is driven by the accumulation of mutations and abnormal DNA methylation patterns, particularly the hypermethylation of tumor-suppressor genes. Changes in genomic DNA methylation patterns are established by the DNA methyltransferases (DNMTs) family: DNMT1, DNMT3a and DNMT3b. The DNMTs are known to be overexpressed in tumors. However, when the DNMTs expression profile is altered in earlier stages of carcinogenesis remains to be elucidated. The resistant hepatocyte model (RHM) allows the analysis of the hepatocellular carcinoma (HCC) from the formation of altered cell foci to the appearance of tumors in rats. To investigate the DNMTs expression in this model, we first observed that timp3, rassf1a and p16 genes became methylated during cancer development by methylation-specific PCR (MSP) and the bisulphate sequencing PCR (BSP) of timp3. The differential expression at the RNA and protein level of the three DNMTs was also assessed. dnmt1 expression was higher in tumors than in normal and early cancer stages. However, no evident overexpression of the enzyme was identified by immunohistochemistry. By contrast, DNMT3a and DNMT3b were consistently subexpressed in tumors. In the present study, we report a carcinogenesis model that does not feature the overexpression of DNMT1 but exhibits a transient expression of DNMT3a and DNMT3b.
ISSN:	1021-335X 1791-2431
DOI:	10.3892/or.2014.3462