| First Author | Zane L | Year | 2012 |
| Journal | Retrovirology | Volume | 9 |
| Pages | 114 | PubMed ID | 23256545 |
| Mgi Jnum | J:317502 | Mgi Id | MGI:6855129 |
| Doi | 10.1186/1742-4690-9-114 | Citation | Zane L, et al. (2012) Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis. Retrovirology 9:114 |
| abstractText | BACKGROUND: 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. RESULTS: 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 p53 -/- genotype). Thus, we find statistically significant differences in tumorigenesis between Tax+p53 +/+ versus Tax+p53 -/- mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, Tax+Wip1 -/- mice show statistically significant reduced prevalence of tumorigenesis compared to Tax+Wip1 +/+ counterparts. CONCLUSIONS: Our findings provide new insights into contributions by p53 and Wip1 in the in vivo oncogenesis of Tax-induced tumors in mice. |
