研究人员通过追踪p16的激活情况，他们发现，老年小鼠（右）比年轻小鼠（左）发的光更亮。
近日，美国北卡罗来纳大学综合癌症中心的研究人员近日借助基因技术培育出了发光小鼠，可用于追踪小鼠的肿瘤生长情况以及衰老过程。
当这些小鼠体内正常的p16基因被激活时，小鼠体内的萤火虫基因就会打开，从而使小鼠发光。据悉，p16INK4a（P16）基因能够激活一种被称为“细胞衰老”的重要的肿瘤抵抗机制，从而在衰老和癌症的抑制方面起到了重要作用。
在这些小鼠的整个生命期内，研究人员只需通过追踪每只小鼠的发光情况，就可研究p16的激活情况。他们发现，老年小鼠比年轻小鼠发的光更亮，而癌症形成的位点则非常明亮，从而使研究人员能够在癌症形成的最早期阶段进行诊断。此项研究的负责人诺曼·夏普里斯（Norman Sharpless）说：“有了这些小鼠，我们就能实时地观察细胞衰老的过程，而且能够真实地观察到活的小鼠体内癌症和衰老最早期的分子阶段。”
该研究小组认为，可以开发出类似的方法来研究人类的衰老和肿瘤形成。
Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
Christin E. Burd, Jessica A. Sorrentino, Kelly S. Clark, David B. Darr, Janakiraman Krishnamurthy, Allison M. Deal, Nabeel Bardeesy, Diego H. Castrillon, David H. Beach, Norman E. Sharpless
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.
文献链接：Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
