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PMID: 2323335 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA.

The EMBO journal ·Vol. 9 ·No. 4 ·1990-04-00 ·Pages 1137-45

Höhne M, Schaefer S, Seifer M, Feitelson MA, Paul D, Gerlich WH

Abstract

Persistent infection by hepatitis B virus (HBV) is epidemiologically correlated with the prevalence of hepatocellular carcinoma, but its role in tumor development is not yet understood. To study the putative oncogenic potential of HBV, a non-malignant immortal mouse hepatocyte line FMH202 harboring metallothionein promoter-driven simian virus 40 large tumor antigen was transfected with HBV DNA. All stably transfected clones which replicated HBV displayed malignant growth characteristics in soft agar and were tumorigenic upon inoculation in nude mice. The nude mice tumors were histologically classified as differentiated or anaplastic hepatocellular carcinomas. As with human liver carcinomas, rearrangements of in vitro integrated HBV sequences were observed in the nude mouse tumors, and in tumor-derived cell lines. In one case, expression of viral core and surface antigens was blocked in the tumors, correlating with hypermethylation of the HBV genome. However, the expression of X gene was maintained in most tumors and tumor-derived cell lines. X protein was detected in nuclei by immune fluorescence and by immune blot. These results provide the first demonstration that HBV displays oncogenic potential in an experimental system. This system could be useful to functionally identify HBV genes which convey a tumorigenic phenotype.

MeSH Terms
Animals Blotting, Northern Blotting, Southern Cell Line Cell Transformation, Neoplastic Clone Cells DNA, Viral/genetics Gene Amplification Gene Rearrangement Genes, Viral Hepatitis B virus/genetics Liver/pathology Liver Neoplasms, Experimental/genetics,microbiology,pathology Mice Plasmids Restriction Mapping Transfection
Chemicals
DNA, Viral
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Höhne M
Department of Pharmacology and Toxicology II, University of Göttingen, FRG.
Schaefer S
Seifer M
Feitelson M A
Paul D
Gerlich W H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-04-00
Pages
1137-45
Language
English
Region
England
NLM ID
8208664
PMCID
PMC551789
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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