Abstract

The relationship between HBV infection and the induction of hepatocellular carcinoma is currently enigmatic. We will explore several mechanisms that might account for association of HBV infection and liver tumor formation. We have observed instability in the genome of the host presenting with hepatocellular carcinoma and in chronic carriers of HBV. We therefore propose to explore the possibilities that HBV might integrate in specific areas of the host genome predisposed to instability that HBV might induce such genome destablization or that environmental factors or hereditary factors are at the root of the instability observed. Further, we propose to determine if genome instability is of predictive value in these tumors. We have established a panel of hepatocellular carcinoma-derived cell lines of hepatocyte morphology and function and plan to continue our analysis of their common chromosome aberrations. We propose to determine specific breakpoints common to these cell lines to identify specific areas of the genome which may contain genes responsible for the control of hepatocyte proliferation. By analysis of somatic cell hybrids, derived from fusion of human hepatocellular carcinoma-derived cell lines and stationary cultures of rat hepatocytes, and transfection of the stationary rat hepatocyte with cloned HBV and human hepatocellular carcinoma-derived DNA, we plan to distinguish between the direct oncogenic potenital of HBV and that of potentially activated human genes. Furthermore, identifiecation of a gene(s) of a gene product(s) that might effect such transformation is proposed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037225-07
Application #
3175029
Study Section
Virology Study Section (VR)
Project Start
1984-06-01
Project End
1992-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Livezey, K W; Negorev, D; Simon, D (2000) Hepatitis B virus-transfected Hep G2 cells demonstrate genetic alterations and de novo viral integration in cells replicating HBV. Mutat Res 452:163-78
Hammond, C; Jeffers, L; Carr, B I et al. (1999) Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma. Hepatology 29:1479-85
Przyborski, S A; Knowles, B B; Ackerman, S L (1998) Embryonic phenotype of Unc5h3 mutant mice suggests chemorepulsion during the formation of the rostral cerebellar boundary. Development 125:41-50
Przyborski, S A; Damjanov, I; Knowles, B B et al. (1998) Differential expression of the zinc finger gene TCF17 in testicular tumors. Cancer Res 58:4598-601
Przyborski, S A; Knowles, B B; Handel, M A et al. (1998) Differential expression of the zinc finger gene Zfp105 during spermatogenesis. Mamm Genome 9:758-62
Oh, B; Hampl, A; Eppig, J J et al. (1998) SPIN, a substrate in the MAP kinase pathway in mouse oocytes. Mol Reprod Dev 50:240-9
Hwang, S Y; Oh, B; Fuchtbauer, A et al. (1997) Maid: a maternally transcribed novel gene encoding a potential negative regulator of bHLH proteins in the mouse egg and zygote. Dev Dyn 209:217-26
Oh, B; Hwang, S Y; Solter, D et al. (1997) Spindlin, a major maternal transcript expressed in the mouse during the transition from oocyte to embryo. Development 124:493-503
Heyer, B S; Warsowe, J; Solter, D et al. (1997) New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo. Mol Reprod Dev 47:148-56
Hwang, S; Benjamin, L E; Oh, B et al. (1996) Genetic mapping and embryonic expression of a novel, maternally transcribed gene Mem3. Mamm Genome 7:586-90

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