Expression of p16INK4a prevents cancer and promotes aging in lymphocytes
- 24 March 2011
- journal article
- Published by American Society of Hematology in Blood
- Vol. 117 (12), 3257-3267
- https://doi.org/10.1182/blood-2010-09-304402
Abstract
Previous authors have suggested that tumor suppressor expression promotes aging while preventing cancer, but direct experimental support for this cancer-aging hypothesis has been elusive. Here, by using somatic, tissue-specific inactivation of the p16INK4a tumor suppressor in murine T- or B-lymphoid progenitors, we report that ablation of p16INK4a can either rescue aging or promote cancer in a lineage-specific manner. Deletion of p16INK4a in the T lineage ameliorated several aging phenotypes, including thymic involution, decreased production of naive T cells, reduction in homeostatic T-cell proliferation, and attenuation of antigen-specific immune responses. Increased T-cell neoplasia was not observed with somatic p16INK4a inactivation in T cells. In contrast, B lineage–specific ablation of p16INK4a was associated with a markedly increased incidence of systemic, high-grade B-cell neoplasms, which limited studies of the effects of somatic p16INK4a ablation on B-cell aging. Together, these data show that expression of p16INK4a can promote aging and prevent cancer in related lymphoid progeny of a common stem cell.This publication has 51 references indexed in Scilit:
- Somatic p16INK4a loss accelerates melanomagenesisOncogene, 2010
- Genome-wide association study identifies five new breast cancer susceptibility lociNature Genetics, 2010
- Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia riskNature Genetics, 2010
- Genome-wide association study identifies three loci associated with melanoma riskNature Genetics, 2009
- Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibilityNature Genetics, 2009
- Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and ArfPublished by Cold Spring Harbor Laboratory ,2008
- Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiencyNature, 2008
- Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primatesProceedings of the National Academy of Sciences of the United States of America, 2007
- Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageingNature, 2006
- Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemiaProceedings of the National Academy of Sciences of the United States of America, 2006