Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
Cette étude présente un modèle murin caractérisé par une activation du gène p16/INK4a à l'intérieur des cellules tumorales et des cellules stromales environnantes
Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16LUC), which faithfully reports expression of p16INK4a, 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 p16INK4a 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 p16LUC was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16INK4a was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16INK4a activation is a characteristic of all emerging cancers, making the p16LUC allele a sensitive, unbiased reporter of neoplastic transformation.
º Activation of cellular senescence with aging does not predict cancer mortality
º p16LUC detects emerging tumors in 14 genetically distinct tumor models
º p16LUC provides a detection advantage over other in vivo cancer monitoring systems
º Both the tumor and stroma of emerging neoplasms express high levels of p16INK4a
P16INK4a-luciferase marks senescent cells in aging mice. Unexpectedly, its expression also marks the formation of all tested spontaneous cancers, revealing the p16LUC mouse model as an exceedingly sensitive reporter of neoplastic transformation.
Cell , résumé, 2012