Histone modification enzymes induced during chemical hepatocarcinogenesis.
Aberrant methylation patterns of genomic DNA are well-studied epigenetic mutations in cancer. Hypermethylation of CpG islands in tumor-suppressor genes promotes oncogenesis and hypomethylation of global genomic DNA affects genomic stability. Cancer is recognized as a genetic and epigenetic disease. However, it is not clear how epigenetic regulatory factors, including histone modification enzymes, chromatin components and other factors are involved in carcinogenesis. To gain insights into the molecular mechanisms mediated by these factors at the early stage of hepatocarcinogenesis and hepatotoxicity induced by chemicals, we investigated gene expression profiles by DNA microarray and Western blot analyses. We prepared RNA and nuclear extracts from livers with hyperplastic nodules expressing Glutathione S-transferase placental form (GST-P) and compared findings with those of normal liver. GST-P is a phase II detoxification enzyme and a well-known tumor marker. We identified several epigenetic regulatory factors that showed dysregulated expression during chemically induced hepatocarcinogenesis. Here I review the characterization and functions of these factors and discuss the mechanisms of tumor marker gene expression during chemical hepatocarcinogenesis.
Osada
Shigehiro
S
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. osada@phar.nagoya-cu.ac.jp
D000818:Animals; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics; D002843:Chromatin / Q000502:physiology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor; D002843:Chromatin; D006657:Histones; D051548:Histone Acetyltransferases; D005982:Glutathione Transferase; D006655:Histone Deacetylases