title: Regulatory mechanism of glutathione S-transferase P-form during chemical hepatocarcinogenesis: old wine in a new bottle.
abstract: The expression of glutathione S-transferase P-form (GST-P) is markedly up-regulated in the initial phase of chemical hepatocarcinogenesis. It is unlikely that a specific genetic change is associated with this common response to a variety of carcinogens. Here, we describe how GST-P gene expression is induced by carcinogenic treatment, focusing on the changes in the network of liver-enriched transcription factors, including CCAAT/enhancer-binding proteins. Although the balance of positive and negative transcription factors regulates the expression of the GST-P gene, additional factors such as the altered regulation of growth control may certainly be necessary for these cells to develop into preneoplastic foci. Furthermore, our genetic analyses on the tumor susceptibility of (F344 x DRH)F2 rats support the hypothesis that the formation of GST-P-positive lesions is required but is not directly associated with final malignant transformation.
authors.affiliation: Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Yoshidakonoe, Sakyoku, Kyoto 606-8501, Japan. ken.higashi@mitsubishicorp.com
authors.forename: Ken
authors.initials: K
authors.lastname: Higashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
authors.forename: Taneaki
authors.initials: T
authors.lastname: Higashi
authors.forename: Masami
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D005982:Glutathione Transferase