| First Author | Ruiz S | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 12 | Pages | e8229 |
| PubMed ID | 20011522 | Mgi Jnum | J:155962 |
| Mgi Id | MGI:4418401 | Doi | 10.1371/journal.pone.0008229 |
| Citation | Ruiz S, et al. (2009) The use of knockout mice reveals a synergistic role of the Vav1 and Rasgrf2 gene deficiencies in lymphomagenesis and metastasis. PLoS One 4(12):e8229 |
| abstractText | BACKGROUND: Vav1 and RasGRF2 are GDP/GTP exchange factors for Ras superfamily GTPases with roles in the development and/or effector functions of T-lymphocytes. METHODOLOGY/PRINCIPAL FINDINGS: Given that the phenotype of Vav1(-/-), Rasgrf2(-/-) and Vav1(-/-);Rasgrf2(-/-) mice has been studied so far in young animals, we decided to explore the long-term consequences of the inactivation of those loci in the immune system. Unexpectedly, our studies revealed that the inactivation of the Vav1 proto-oncogene favors the formation of lymphoblastic lymphoma-like tumors in aging mice. Those tumors, that can be found either localized exclusively inside the thymus or widely disseminated in hematopoietic and non-hematopoietic tissues, are composed of CD3(+) lymphoblasts that display heterogeneous combinations of CD4 and CD8 surface markers. Interestingly, the additional deletion of the Rasgrf2 gene induces a shortening in the latency period for the development of those tumors, an increase in the percentage of disseminated tumors outside the thymus and, as a result, higher mortality rates. CONCLUSIONS/SIGNIFICANCE: These data reveal unexpected negative roles for Vav1 and RasGRF2 in different stages of T-cell lymphoma progression. They also suggest that the inactivation of Vav1 function may represent an inadequate strategy to treat T-cell lymphomas, especially those associated with low levels of Rasgrf2 gene expression. |
