Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model: A sequential pathological evaluation.
BACKGROUND
The introduction of transgenic technology has made it possible to study the steps of carcinogenesis and directly establish the link between viral subgenomic fragments and specific types of cancer. Research directed at hepatitis B virus (HBV)-related carcinogenesis has benefited from this technology. We present a detailed pathological evaluation of the sequential steps of hepatocarcinogenesis in a hepatitis B 'x' (HBx) transgenic mouse model. In this model, the transgene incorporates the region encoding amino acids 58-154 of the HBV X protein and the murine c-myc gene. This model demonstrated changes in the liver from birth with foci of multicentric dysplasia evolving into nodules and overt hepatocellular carcinoma between 20 and 28 weeks.


RESULTS
The hepatocytes were mitotically active and showed increased proliferative capacity soon after birth, with exponential increase thereafter. This was accompanied by a high rate of apoptosis, which later declined as the tumors developed. Other functional and immunophenotypic characteristics included a high c-myc expression in the neoplastic lesions, no alteration in p53 expression, and no alteration in the expression of hepatic enzymes except for diffuse expression of succinic dehydrogenase.


CONCLUSIONS
The entire process illustrates the disturbances of cell growth and death because of the collaborative influence of HBx and c-myc genes that result in the development of hepatocellular carcinoma after a prolonged latent period.
Lakhtakia
Ritu
R
Department of Pathology, All India Institute of Medical Sciences, Aruna Asaf Ali Marg, New Delhi, India.
Kumar
Vijay
V
Reddi
Honey
H
Mathur
Meera
M
Dattagupta
Siddhartha
S
Panda
Subrat Kumar
SK
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D002455:Cell Division; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016259:Genes, myc; D006651:Histocytochemistry; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008854:Microscopy, Electron; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
D016326:Extracellular Matrix Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein