INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53

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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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