Expression of p16(INK4a) prevents cancer and promotes aging in lymphocytes.
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.
Department of Genetics, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, NC 27599-7295, USA.
Yan
Y
Liu
Soren M
SM
Johnson
Yuri
Y
Fedoriw
Arlin B
AB
Rogers
Hong
H
Yuan
Janakiraman
J
Krishnamurthy
Norman E
NE
Sharpless
D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D019426:Integrases / Q000235:genetics / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D054503:Lymphoid Progenitor Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009928:Organ Specificity / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C045073:Cre recombinase; D019426:Integrases
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