WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?
| Autor: | Luc Willems, Alexandre Carpentier, Pierre-Yves Barez, Nicolas Gillet |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
p53
lcsh:Immunologic diseases. Allergy Phosphatase T-cell leukemia Tax Wip1 Chk2 medicine.disease_cause DNA damage response Mediator HBZ MDM2 Virology hemic and lymphatic diseases medicine Phosphoprotein Phosphatases Animals Humans Phosphoprotein phosphatase biology Research Gene Products tax PPM1D Cell Transformation Viral Infectious Diseases Cell Transformation Neoplastic Virus type HTLV-1 ATM Immunology biology.protein Mdm2 Genomic stress Antibody Tumor Suppressor Protein p53 Carcinogenesis lcsh:RC581-607 |
| Zdroj: | Retrovirology Retrovirology, Vol 9, Iss 1, p 115 (2012) |
| ISSN: | 1742-4690 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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