Department of Animal Medicine and Surgery, Veterinary School, Complutense University, Madrid, Spain.
Lab Invest. 2011 Nov;91(11):1634-42. doi: 10.1038/labinvest.2011.133. Epub 2011 Aug 29.
The cell cycle inhibitors p21(Waf1/Cip1) and p27(Kip1) are frequently downregulated in many human cancers, and correlate with a worse prognosis. We show here that combined deficiency in p21 and p27 proteins in mice is linked to more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The most common tumors developed in p21p27 double-null mice were endocrine, with a higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas. The combined absence of p21 and p27 proteins delays the incidence of radiation-induced thymic lymphomas with a higher apoptotic rate, measured by active caspase-3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in mice.
细胞周期抑制剂 p21(Waf1/Cip1)和 p27(Kip1)在许多人类癌症中经常下调，与预后不良相关。我们在这里表明，在小鼠中同时缺乏 p21 和 p27 蛋白与更具侵袭性的自发性肿瘤发生有关，导致寿命缩短。p21p27 双基因敲除小鼠最常见的肿瘤为内分泌肿瘤，垂体腺瘤、嗜铬细胞瘤和甲状腺腺瘤的发病率更高。p21 和 p27 蛋白的联合缺失会延迟辐射诱导的胸腺淋巴瘤的发生，通过活性 caspase-3 和 cleaved PARP-1 的免疫表达来衡量，其凋亡率更高。这些结果为这两种细胞周期依赖性激酶抑制剂在小鼠肿瘤发生中的合作提供了实验证据。
