Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma
Berasain C, Hevia H, Fernández-Irigoyen J, Larrea E, Caballería J, Mato JM, Prieto J, Corrales FJ, García-Trevijano ER, Avila MA.
Division of Hepatology and Gene Therapy, CIMA, Facultad de Medicina, Universidad de Navarra. 31008 Pamplona, Spain
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and adenine salvage pathways. In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma.
Deficient MTAP gene expression has been recognized in many transformed cell lines and tissues. In the present work, we have studied the expression of MTAP in human and experimental liver cirrhosis and hepatocarcinoma. We observe that MTAP gene expression is significantly reduced in human hepatocarcinoma tissues and cell lines. Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients. We provide evidence indicating that epigenetic mechanisms, involving DNA methylation and histone deacetylation, may play a role in the silencing of MTAP gene expression in hepatocarcinoma.
Given the recently proposed tumor suppressor activity of MTAP, our observations can be relevant to the elucidation of the molecular mechanisms of multistep hepatocarcinogenesis.
CITATION Biochim Biophys Acta. 2004 Nov 5;1690(3):276-84