An unexpected role for p53 in augmenting SV40 large T antigen-mediated tumorigenesis

被引:22
作者
Herzig, M [1 ]
Novatchkova, M [1 ]
Christofori, G [1 ]
机构
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
关键词
SV40 large T antigen; transgenic mice; tumorigenesis; tumor suppressor p53;
D O I
10.1515/BC.1999.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:203 / 211
页数:9
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