Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis
<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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-12-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/9/1/114 |
| _version_ | 1818211064937971712 |
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| author | Zane Linda Yasunaga Junichiro Mitagami Yu Yedavalli Venkat Tang Sai-Wen Chen Chia-Yen Ratner Lee Lu Xiongbin Jeang Kuan-Teh |
| author_facet | Zane Linda Yasunaga Junichiro Mitagami Yu Yedavalli Venkat Tang Sai-Wen Chen Chia-Yen Ratner Lee Lu Xiongbin Jeang Kuan-Teh |
| author_sort | Zane Linda |
| collection | DOAJ |
| description | <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> |
| first_indexed | 2024-12-12T05:26:34Z |
| format | Article |
| id | doaj.art-3db76394251c4c5ba2f12d757f5d2c91 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-12T05:26:34Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-3db76394251c4c5ba2f12d757f5d2c912022-12-22T00:36:26ZengBMCRetrovirology1742-46902012-12-019111410.1186/1742-4690-9-114Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesisZane LindaYasunaga JunichiroMitagami YuYedavalli VenkatTang Sai-WenChen Chia-YenRatner LeeLu XiongbinJeang Kuan-Teh<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>http://www.retrovirology.com/content/9/1/114 |
| spellingShingle | Zane Linda Yasunaga Junichiro Mitagami Yu Yedavalli Venkat Tang Sai-Wen Chen Chia-Yen Ratner Lee Lu Xiongbin Jeang Kuan-Teh Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis Retrovirology |
| title | Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis |
| title_full | Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis |
| title_fullStr | Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis |
| title_full_unstemmed | Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis |
| title_short | Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis |
| title_sort | wip1 and p53 contribute to htlv 1 tax induced tumorigenesis |
| url | http://www.retrovirology.com/content/9/1/114 |
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