Accelerated development of polyoma tumors and embryonic lethality: Different effects of p53 loss on related mouse backgrounds

Dilip C. Dey, Roderick P. Bronson, Jean Dahl, John P. Carroll, Thomas L. Benjamin

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Molecular evidence linking polyoma virus to p53 inactivation is thus far lacking, setting this highly oncogenic virus apart from other DNA tumor viruses. As a biological test for interaction, we studied the effects of p53 loss on development of virus-induced tumors. The absence of p53 led to more rapid tumor development on two different mouse backgrounds, indicating synergism between p53 loss and oncogenic pathways controlled directly by the virus. No effects of p53 on tumor type or frequency were noted. Polyoma tumor-derived cells in culture retained p53, and most of these showed induction of p21(CIP1/WAF1) in response to DNA damage. These results indicate that p53 functions are not directly and fully impaired by the virus in the intact host. On one mouse background, it was discovered that loss of p53 resulted in complete embryonic lethality prior to 11 days of gestation. This lethality could be rescued by inclusion of gene(s) from a 129/SvJ background.

Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalCell Growth and Differentiation
Volume11
Issue number5
StatePublished - May 2000
Externally publishedYes

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