First Author | Liu Y | Year | 2011 |
Journal | Blood | Volume | 117 |
Issue | 12 | Pages | 3257-67 |
PubMed ID | 21245485 | Mgi Jnum | J:170512 |
Mgi Id | MGI:4946592 | Doi | 10.1182/blood-2010-09-304402 |
Citation | Liu Y, et al. (2011) Expression of p16INK4a prevents cancer and promotes aging in lymphocytes. Blood 117(12):3257-67 |
abstractText | 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. |