p16（INK4a）和p53缺陷在肿瘤发生过程中相互协作。

p16(INK4a) and p53 deficiency cooperate in tumorigenesis.

作者信息

Sharpless Norman E, Alson Scott, Chan Suzanne, Silver Daniel P, Castrillon Diego H, DePinho Ronald A

机构信息

Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street (M413), Boston, MA 02115, USA.

出版信息

Cancer Res. 2002 May 15;62(10):2761-5.

PMID:12019151

Abstract

The combined impact of mutations in p16(INK4a) and p53 was examined in cellular growth,transformation, and tumor formation. In cultured cells, p16(INK4a) loss enhanced growth at high density and conferred susceptibility to oncogene-induced transformation. In vivo, mice doubly deficient for p16(INK4a) and p53 showed an increased rate of tumor formation with particular susceptibility to aggressive angiosarcomas. Furthermore, p16(INK4a) silencing by promoter methylation was detected in tumors derived from p16(INK4a+/-) and (+/+) mice, independent of p53 status. These data suggest at least one general feature of malignancy, resistance to density-mediated growth arrest depends on p16(INK4a) rather than p53. This cooperation between p16(INK4a) and p53 loss in tumorigenesis is consistent with the view that these genes function in distinct anticancer pathways.

摘要

研究了p16（INK4a）和p53突变在细胞生长、转化及肿瘤形成方面的联合影响。在培养细胞中，p16（INK4a）缺失增强了高密度下的生长，并赋予了对癌基因诱导转化的易感性。在体内，p16（INK4a）和p53双缺陷的小鼠显示出肿瘤形成率增加，对侵袭性血管肉瘤具有特殊易感性。此外，在源自p16（INK4a+/-）和（+/+）小鼠的肿瘤中检测到通过启动子甲基化导致的p16（INK4a）沉默，与p53状态无关。这些数据表明恶性肿瘤的至少一个普遍特征，即对密度介导的生长停滞的抗性取决于p16（INK4a）而非p53。p16（INK4a）和p53缺失在肿瘤发生中的这种协同作用与这些基因在不同抗癌途径中发挥作用的观点一致。