TY - JOUR
T1 - Monitoring tumorigenesis and senescence in vivo with a p16 INK4a-luciferase model
AU - Burd, Christin E.
AU - Sorrentino, Jessica A.
AU - Clark, Kelly S.
AU - Darr, David B.
AU - Krishnamurthy, Janakiraman
AU - Deal, Allison M.
AU - Bardeesy, Nabeel
AU - Castrillon, Diego H.
AU - Beach, David H.
AU - Sharpless, Norman E.
PY - 2013/1/7
Y1 - 2013/1/7
N2 - 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 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 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 p16 LUC allele a sensitive, unbiased reporter of neoplastic transformation.
AB - 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 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 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 p16 LUC allele a sensitive, unbiased reporter of neoplastic transformation.
UR - http://www.scopus.com/inward/record.url?scp=84872569990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872569990&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.12.010
DO - 10.1016/j.cell.2012.12.010
M3 - Article
C2 - 23332765
AN - SCOPUS:84872569990
SN - 0092-8674
VL - 152
SP - 340
EP - 351
JO - Cell
JF - Cell
IS - 1-2
ER -