| First Author | Schmitt CA | Year | 1999 |
| Journal | Genes Dev | Volume | 13 |
| Issue | 20 | Pages | 2670-7 |
| PubMed ID | 10541553 | Mgi Jnum | J:58293 |
| Mgi Id | MGI:1347178 | Doi | 10.1101/gad.13.20.2670 |
| Citation | Schmitt CA, et al. (1999) INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev 13(20):2670-7 |
| abstractText | The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products. To compare the impact of these loci on tumor development and treatment response, the Emu-myc transgenic lymphoma model was used to generate genetically defined tumors with mutations in the INK4a/ARF, Rb, or p53 genes. Like p53 null lymphomas, INK4a/ARF null lymphomas formed rapidly, were highly invasive, displayed apoptotic defects, and were markedly resistant to chemotherapy in vitro and in vivo. Furthermore, INK4a/ARF(-/-) lymphomas displayed reduced p53 activity despite the presence of wild-type p53 genes. Consequently, INK4a/ARF and p53 mutations lead to aggressive tumors by disrupting overlapping tumor suppressor functions. These data have important implications for understanding the clinical behavior of human tumors. |
