Quantifying growth and transformation frequency of oncogene-expressing mouse hepatocytes in vivo

Marxa L. Figueiredo, Kristin M. Wentworth, Eric P. Sandgren

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Gene changes can affect cancer cells in many ways, but changes that increase disease severity - by allowing cells to proliferate when they should be quiescent, by enhancing their rate of growth under growth permissive conditions, or by increasing the risk that they will accumulate additional carcinogenic alterations - must be identified so that strategies to counter their effects can be developed. We describe a novel in vivo assay system based on hepatocyte transplantation that permits us to accomplish this objective for genetically modified hepatocytes. We find that the oncogenes c-myc and transforming growth factor a, but not simian virus 40 T-antigen, increase the rate of hepatocyte growth under growth permissive conditions. However, no single oncogene can induce hepatocyte growth in quiescent liver. In contrast, at least one oncogene combination, transforming growth factor α/ T-antigen, was sufficient to direct cell autonomous growth even in this nonpermissive environment. Furthermore, we could quantify risk for progression to neoplasia associated with oncogene expression; increased transformation frequency was the principal carcinogenic effect of T-antigen. Conclusion: This system identifies biological mechanistic role(s) in carcinogenesis for candidate genetic changes implicated in development of human liver cancer. The quantitative and comparative evaluation of gene effects on liver cancer allows us to prioritize targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)634-643
Number of pages10
JournalHepatology
Volume52
Issue number2
DOIs
StatePublished - Aug 2010
Externally publishedYes

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Oncogenes
Hepatocytes
Viral Tumor Antigens
Growth
Transforming Growth Factors
Liver Neoplasms
myc Genes
Simian virus 40
Human Development
Genes
Neoplasms
Carcinogenesis
Transplantation
Liver

ASJC Scopus subject areas

  • Hepatology

Cite this

Quantifying growth and transformation frequency of oncogene-expressing mouse hepatocytes in vivo. / Figueiredo, Marxa L.; Wentworth, Kristin M.; Sandgren, Eric P.

In: Hepatology, Vol. 52, No. 2, 08.2010, p. 634-643.

Research output: Contribution to journalArticle

Figueiredo, Marxa L. ; Wentworth, Kristin M. ; Sandgren, Eric P. / Quantifying growth and transformation frequency of oncogene-expressing mouse hepatocytes in vivo. In: Hepatology. 2010 ; Vol. 52, No. 2. pp. 634-643.
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