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

Summary 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.