Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.
Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.
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DOI：
10.1016/j.cell.2012.12.010
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发表时间：
2013-01-17
期刊：
影响因子：
64.5
通讯作者：
Sharpless NE
中科院分区：
文献类型：
--
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
在体内监测癌症和衰老仍然具有实验挑战性。在这里，我们描述了一个荧光素酶敲入小鼠（p16 LUC），它忠实地报告表达p16 INK 4a，肿瘤抑制和衰老的生物标志物。在p16+/LUC小鼠的发光的终身评估显示，随着年龄的增长，这是高度可变的同期圈养，同基因小鼠的队列指数增加。p16 INK 4a的表达与衰老并不能预测癌症的发展，这表明衰老细胞的积累并不是癌症相关死亡的主要决定因素。在14个测试的肿瘤模型中，p16 LUC的表达被早期肿瘤事件局部激活，使肿瘤的可视化灵敏度超过其他成像方式。p16 INK 4a的激活在新出现的肿瘤和周围的基质细胞中被注意到。这项工作表明，p16 INK 4a激活是所有新兴癌症的特征，使p16 LUC等位基因成为肿瘤转化的敏感，无偏见的报告者。
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.
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影响因子：
3.7
作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
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通讯作者：
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