Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model

A sequential pathological evaluation

Ritu Lakhtakia, Vijay Kumar, Honey Reddi, Meera Mathur, Siddhartha Dattagupta, Subrat Kumar Panda

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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. Methods and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)80-91
Number of pages12
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume18
Issue number1
DOIs
Publication statusPublished - 2003

Fingerprint

myc Genes
Hepatitis B
Transgenic Mice
Hepatocellular Carcinoma
Carcinogenesis
Parturition
Technology
Succinate Dehydrogenase
Liver
Transgenes
Hepatitis B virus
Hepatocytes
Neoplasms
Cell Death
Apoptosis
Amino Acids
Enzymes
Growth
Research
hepatitis B virus X protein

Keywords

  • Experimental hepatocarcinogenesis
  • Hepatitis B virus
  • Transgenesis

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model : A sequential pathological evaluation. / Lakhtakia, Ritu; Kumar, Vijay; Reddi, Honey; Mathur, Meera; Dattagupta, Siddhartha; Panda, Subrat Kumar.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 18, No. 1, 2003, p. 80-91.

Research output: Contribution to journalArticle

Lakhtakia, Ritu ; Kumar, Vijay ; Reddi, Honey ; Mathur, Meera ; Dattagupta, Siddhartha ; Panda, Subrat Kumar. / Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model : A sequential pathological evaluation. In: Journal of Gastroenterology and Hepatology (Australia). 2003 ; Vol. 18, No. 1. pp. 80-91.
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