molecular mechanisms underlying hepatocellular carcinoma肝细胞癌的分子机制.pdfVIP

Viruses 2009, 1, 852-872; doi:10.3390/v1030852 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Molecular Mechanisms Underlying Hepatocellular Carcinoma Philippe Merle 1,* and Christian Trepo 2 1 INSERM, U871, 69003 Lyon; Université Lyon 1, IFR62 Lyon-Est, 69008 Lyon, France 2 Hospices Civils de Lyon, Hôtel Dieu, Service d’hépatologie et de gastroentérologie, 69002 Lyon, France; E-Mail: christian.trepo@inserm.fr * Author to whom correspondence should be addressed; E-Mails: philippe.merle@inserm.fr; Tel.: +33 4 72 68 19 54; Fax: +33 4 72 68 19 71. Received: 14 August 2009; in revised form: 3 November 2009 / Accepted: 9 November 2009 / Published: 9 November 2009 Abstract: Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involvi