Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model

被引：308

作者：

Burd, Christin E. ^{[1
,2
,3
]}

Sorrentino, Jessica A. ^{[3
]}

Clark, Kelly S. ^{[1
,2
,3
]}

Darr, David B. ^{[1
,2
,3
]}

Krishnamurthy, Janakiraman ^{[1
,2
,3
]}

Deal, Allison M. ^{[3
]}

Bardeesy, Nabeel ^{[4
]}

Castrillon, Diego H. ^{[5
]}

Beach, David H. ^{[6
]}

Sharpless, Norman E. ^{[1
,2
,3
]}

机构：

[1] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Boston, MA 02114 USA

[5] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[6] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, London E1 2AT, England

来源：

CELL | 2013年 / 152卷 / 1-2期

关键词：

P16(INK4A) TUMOR-SUPPRESSOR; CELLULAR SENESCENCE; FIBROBLAST SENESCENCE; METASTATIC MELANOMA; TRANSGENIC MICE; STEM-CELLS; LIFE-SPAN; T-CELLS; EXPRESSION; CANCER;

D O I：

10.1016/j.cell.2012.12.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：340 / 351

页数：12

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