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- Title
The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with γ-radiation-induced T-cell lymphoblastic lymphomas.
- Authors
Santos, J.; González-Sánchez, L.; Villa-Morales, M.; Ors, I.; López-Nieva, P.; Vaquero, C.; González-Gugel, E.; Fernández-Navarro, P.; Roncero, A. M.; Guenet, J.-L.; Montagutelli, X.; Fernández-Piqueras, J.
- Abstract
Using an inter-specific subcongenic strain, Nested Recombinant Haplotype 3 (NRH3), generated between two mouse strains showing extreme differences in γ-radiation-induced thymic lymphoma susceptibility (SEG/Pas and C57BL/6J), we have identified a critical region on chromosome 19 that regulates survival of mice suffering from T-cell lymphoblastic lymphomas. Mapped on this region, the gene encoding the Cd274 ligand is able to trigger an inhibitory effect that modulates T-cell receptor (TCR) signalling and affects thymocyte maturation. Interestingly, this gene shows differential expression between thymic stromal cells from both strains in early response to a single sublethal γ-ray dose, but is inhibited in T-cell lymphoblastic lymphomas. Furthermore, we have identified several polymorphisms in the complementary DNA sequence of this gene that affect the affinity for its Cd279 receptor and are able to induce a differential rate of thymocyte apoptosis. Taken together, our data are consistent with Cd274 acting as a genetic modifier that influences the survival of γ-radiation-induced T-cell lymphoma-bearing mice. The data similarly support the idea of a co-evolution of tumour cells and associated stromal cells to generate a favourable microenvironment for T-cell lymphoma growth.
- Subjects
T-cell lymphoma; LYMPHOMAS in children; LABORATORY mice; CARCINOGENESIS; GENE mapping; IMMUNOFLUORESCENCE; APOPTOSIS
- Publication
Oncogene, 2010, Vol 29, Issue 38, p5265
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.280