0000000000744498
AUTHOR
Toshikazu Nakamura
Analysis of the Effects of Modifying Agents on Six Different Phenotypes in Preneoplastic Foci in the Liver in Medium-Term Bioassay Model in Rats
Recently a great deal of interest has been expressed in characterizing the altered enzyme phenotype of putative preneoplastic rat liver lesions. In particular, attention has been given to the changes in drug metabolizing potential, conferring physiological advantage to initiated cells, and their usefulness as marker lesions for the analysis of the development of neoplasia1–2.
Transcription of the MAT2A gene, coding for methionine adenosyltransferase, is up-regulated by E2F and Sp1 at a chromatin level during proliferation of liver cells
Methionine adenosyltransferase (MAT) is an essential enzyme because it catalyzes the formation of S-adenosylmethionine, the main methyl donor. Two MAT-encoding genes (MAT1A, MAT2A) are found in mammals. The latter is expressed in proliferating liver, dedifferentiation and cancer, whereas MAT1A is expressed in adult quiescent hepatocytes. Here, we report studies on the molecular mechanisms controlling the induction of MAT2A in regenerating rat liver and in proliferating hepatocytes. The MAT2A is up-regulated at two discrete moments during liver regeneration, as confirmed by RNApol-ChIP analysis. The first one coincides with hepatocyte priming (i.e. G0-G1 transition), while the second one tak…