Increased Rac activity is required for the progression of T-lymphomas induced by Pten-deficiency
| Autor: | Kristin Strumane, Inge Baas, John G. Collard, Ji-Ying Song |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Biology Lymphoma T-Cell law.invention Mice Phosphatidylinositol 3-Kinases law Animals Guanine Nucleotide Exchange Factors PTEN T-Lymphoma Invasion and Metastasis-inducing Protein 1 Activator (genetics) Cell growth PTEN Phosphohydrolase Hematology Mice Mutant Strains Tumor formation Cell biology Oncology Apoptosis Tumor progression Disease Progression Cancer research biology.protein Suppressor Akt phosphorylation Proto-Oncogene Proteins c-akt Gene Deletion Signal Transduction |
| Zdroj: | Leukemia Research. 32:113-120 |
| ISSN: | 0145-2126 |
| DOI: | 10.1016/j.leukres.2007.03.034 |
| Popis: | Mutation of the tumor suppressor PTEN results in loss of its PI3-kinase counteracting function. PI3-kinase stimulates tumor formation by PKB/Akt-mediated cell proliferation and prevention of apoptosis. PI3-kinase may also activate Rho-GTPases and their regulatory GEFs to promote invasion. Here we have analyzed the function of the Rac-specific activator, Tiam1, in PI3-kinase-induced T-lymphomagenesis. Mice with a T cell-specific Pten deletion developed T-lymphomas with enhanced PKB/Akt phosphorylation. However, these T-lymphomas infiltrated more frequently into various organs in Tiam1-deficient mice compared to wild type mice. Surprisingly, Tiam1-deficient lymphomas showed increased Rac activity, suggesting that the lack of Tiam1 is compensated by alternative Rac-activating mechanisms that lead to increased progression of PI3-kinase-induced T-lymphomas. |
| Databáze: | OpenAIRE |
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