An unexpected role for p53 in augmenting SV40 large T antigen-mediated tumorigenesis.
Simian virus 40 large T antigen transforms cells by sequestration and inactivation of the tumor suppressor proteins p53, retinoblastoma gene product (pRb), and the pRb-related proteins p107 and p130. Thus, the absence of functional p53 is expected to promote T antigen-mediated tumorigenesis. However, in a transgenic mouse model of T antigen-mediated beta cell carcinogenesis (Rip1Tag2), tumor volumes are significantly diminished when these mice are intercrossed with p53-deficient mice. Whereas the incidence of beta tumor cell apoptosis is unaffected, their proliferation rate is reduced in p53-deficient beta cell tumors in vivo and in cell lines established from these tumors in vitro. Biochemical analyses reveal higher levels of T antigen in wild-type tumor cells as compared to p53-deficient tumor cells. The data indicate that p53 stabilizes SV40 large T antigen, thereby augmenting its oncogenic potential as manifested by increased proliferation rates in wild-type beta tumor cells as compared to p53-deficient beta tumor cells.
Herzig
M
M
Research Institute of Molecular Pathology, Vienna, Austria.
Novatchkova
M
M
Christofori
G
G
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53