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Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.

Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16(INK4a) with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16(LUC) was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16(INK4a) was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation.

Pubmed ID: 23332765

Authors

  • Burd CE
  • Sorrentino JA
  • Clark KS
  • Darr DB
  • Krishnamurthy J
  • Deal AM
  • Bardeesy N
  • Castrillon DH
  • Beach DH
  • Sharpless NE

Journal

Cell

Publication Data

January 17, 2013

Associated Grants

  • Agency: NIA NIH HHS, Id: AG024379
  • Agency: NIA NIH HHS, Id: AG036817
  • Agency: NCI NIH HHS, Id: CA137181
  • Agency: NCI NIH HHS, Id: CA163896
  • Agency: NIA NIH HHS, Id: K99 AG036817
  • Agency: NCI NIH HHS, Id: P30 CA016086
  • Agency: NIA NIH HHS, Id: R00 AG036817
  • Agency: NIA NIH HHS, Id: R01 AG024379
  • Agency: NCI NIH HHS, Id: R01 CA137181
  • Agency: NCI NIH HHS, Id: R01 CA163896
  • Agency: NIBIB NIH HHS, Id: R01 EB010023
  • Agency: NIEHS NIH HHS, Id: T32 ES007126

Mesh Terms

  • Aging
  • Animals
  • Biological Markers
  • Cell Aging
  • Cell Transformation, Neoplastic
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Gene Knock-In Techniques
  • Luciferases
  • Mice
  • Neoplasms
  • Wounds and Injuries