| First Author | Santos J | Year | 2010 |
| Journal | Oncogene | Volume | 29 |
| Issue | 38 | Pages | 5265-73 |
| PubMed ID | 20639904 | Mgi Jnum | J:168370 |
| Mgi Id | MGI:4888095 | Doi | 10.1038/onc.2010.280 |
| Citation | Santos J, et al. (2010) The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with gamma-radiation-induced T-cell lymphoblastic lymphomas. Oncogene 29(38):5265-73 |
| abstractText | Using an inter-specific subcongenic strain, Nested Recombinant Haplotype 3 (NRH3), generated between two mouse strains showing extreme differences in gamma-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 gamma-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 gamma-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. |
