title: Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes.
abstract: The multifactorial and multistage pathogenesis of hepatocellular carcinoma (HCC) has fascinated a wide spectrum of scientists for decades. While a number of major risk factors have been identified, their mechanistic roles in hepatocarcinogenesis still need to be elucidated. Many tumor suppressor genes (TSGs) have been identified as being involved in HCC. These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors: the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele. Hepatitis B virus (HBV) is one of the most important risk factors associated with HCC. Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor, one advantage of mouse models for HBV/HCC research is the numerous and powerful genetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs. Here, we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner. Discoveries obtained using mouse models will have a great impact on HCC translational medicine.
authors.affiliation: Yuan-Chi Teng, Ting-Fen Tsai, Program in Molecular Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yuan-Chi
authors.initials: YC
authors.lastname: Teng
authors.affiliation: Yuan-Chi Teng, Ting-Fen Tsai, Program in Molecular Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Shen
authors.affiliation: Yuan-Chi Teng, Ting-Fen Tsai, Program in Molecular Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Cheng-Heng
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Yuan-Chi Teng, Ting-Fen Tsai, Program in Molecular Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Tsai
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000648:ultrastructure / Q000821:virology*; D003043:Cocarcinogenesis; D016147:Genes, Tumor Suppressor; D057895:Haploinsufficiency; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000648:ultrastructure / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics
keywords: Haploinsufficiency; Hepatitis B virus; Hepatocellular carcinoma; Mouse models; Tumor suppressor genes