| Summary: | <p>Abstract</p> <p>Background</p> <p>Human T-cell Leukemia Virus type 1 (HTLV-1) infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL), a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells. All ATLL cases are believed to have reduced p53 activity although only a minority of ATLLs have genetic mutations in their p53 gene. It has been suggested that p53 function is inactivated by the Tax protein.</p> <p>Results</p> <p>Using genetically altered mice, we report here that Tax expression does not achieve a functional equivalence of p53 inactivation as that seen with genetic mutation of p53 (i.e. a <it>p53</it><sup><it>−/−</it></sup> genotype). Thus, we find statistically significant differences in tumorigenesis between <it>Tax</it><sup><it>+</it></sup><it>p53</it><sup><it>+/+</it></sup><it>versus Tax</it><sup><it>+</it></sup><it>p53</it><sup><it>−/−</it></sup> mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, <it>Tax</it><sup><it>+</it></sup><it>Wip</it>1<sup><it>−/−</it></sup> mice show statistically significant reduced prevalence of tumorigenesis compared to <it>Tax</it><sup><it>+</it></sup><it>Wip</it>1<sup><it>+/+</it></sup> counterparts.</p> <p>Conclusions</p> <p>Our findings provide new insights into contributions by p53 and Wip1 in the <it>in vivo</it> oncogenesis of Tax-induced tumors in mice.</p>
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