ROLE OF HEPATITIS B VIRUS IN HEPATACELLULAR CARCINOMA

Project: Research project

Project Details

Description

Hepatitis B virus (HBV) is an agent which infects man, integrates
into the genome of a specific tissue (liver), and probably causes
hepatocellular carcinoma (HCC). In the United States, there are
over three quarters of a million individuals with persistent HBV
infection and worldwide, HCC is one of the leading causes of
death from cancer. The purpose of this proposal is to study the
strategies and molecular mechanisms utilized by the hepatitis B
virus (HBV) to understand its hepatotropism, genetic regulation,
and association with pathologic conditions especially its role in
liver carcinogenesis. Our underlying hypothesis is that the HBV
genome has evolved mechanisms of gene regulation and expression
similar to those utilized by host genes as an adaptation for an
efficient symbiotic relationship with its host. Mouse embryo
microinjection technology has been used to construct an animal
model simulating the chronic carrier state. Such HBV transgenic
mice, in which the newly acquired HBV genome is expressed and
transmitted in kindreds of mice will allow the genetic dissection
of HBV gene expression, regulation, and function. This system
appears ideally suited to examine the influence of host genes on
HBV expression, the developmental regulation of HBV sequences,
and the associated factors potentially linking HBV to the
multistep process of hepatocarcinogenesis. In addition, the viral
genetic requirements for tissue specific expression will be
examined in liver cells in vivo. Such an approach has broad
applicability towards elucidating novel mechanisms of higher
eukaryotic gene expression and regulation. Our program involves
the isolation and characterization of nucleic acids by Southern
blot analysis, Northern blot analysis, primer extension, cloning,
and sequencing. Viral proteins will be identified and studied using
monoclonal antibodies by immunohistochemistry and protein
blotting. Hepatocarcinogenesis studies will examine the
relationship of treating HBV transgenic mice with such agents as
aflatoxin B1 and alcohol upon the development of liver pathology
and the incidence of liver tumors in such mice followed over time.
StatusFinished
Effective start/end date1/1/901/1/90

Funding

  • National Cancer Institute

ASJC

  • Genetics
  • Molecular Biology
  • Oncology
  • Cancer Research
  • Hepatology

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