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| Item Type: | Article |
|---|---|
| Title: | INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53 |
| Creators Name: | Schmitt, C.A., McCurrach, M.E., de Stanchina, E., Wallace-Brodeur, R.R. and Lowe, S.W. |
| Abstract: | 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. |
| Keywords: | Antineoplastic Agents, Apoptosis, Drug Resistance, Genetic Enhancer Elements, myc Genes, p16 Genes, p53 Genes, Immunoglobulin Heavy Chains, Lymphoma, B-Cell, Mutation, Proteins, Tumor Suppressor Protein p14ARF, Animals, Mice |
| Source: | Genes & Development |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Volume: | 13 |
| Number: | 20 |
| Page Range: | 2670-2677 |
| Date: | 15 October 1999 |
| Official Publication: | http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=317110&rendertype=abstract |
| PubMed: | View item in PubMed |
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