| Literature DB >> 21245485 |
Yan Liu1, Soren M Johnson, Yuri Fedoriw, Arlin B Rogers, Hong Yuan, Janakiraman Krishnamurthy, Norman E Sharpless.
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 p16(INK4a) tumor suppressor in murine T- or B-lymphoid progenitors, we report that ablation of p16(INK4a) can either rescue aging or promote cancer in a lineage-specific manner. Deletion of p16(INK4a) 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 p16(INK4a) inactivation in T cells. In contrast, B lineage-specific ablation of p16(INK4a) was associated with a markedly increased incidence of systemic, high-grade B-cell neoplasms, which limited studies of the effects of somatic p16(INK4a) ablation on B-cell aging. Together, these data show that expression of p16(INK4a) can promote aging and prevent cancer in related lymphoid progeny of a common stem cell.Entities:
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Year: 2011 PMID： 21245485 PMCID： PMC3069667 DOI： 10.1182/blood-2010-09-304402
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113