Expression of p16INK4a prevents cancer and promotes aging in lymphocytes
Y Liu, SM Johnson, Y Fedoriw… - Blood, The Journal …, 2011 - ashpublications.org
Y Liu, SM Johnson, Y Fedoriw, AB Rogers, H Yuan, J Krishnamurthy, NE Sharpless
Blood, The Journal of the American Society of Hematology, 2011•ashpublications.orgPrevious 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 …
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 …
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.
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