期刊
CANCER RESEARCH
卷 65, 期 7, 页码 2795-2803出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-1270
关键词
-
类别
资金
- NCI NIH HHS [K08CA71928] Funding Source: Medline
Accelerated cellular senescence (ACS) has been described for tumor cells treated with chemotherapy and radiation. Following exposure to genotoxins, tumor cells undergo terminal growth arrest and adopt morphologic and marker features suggestive of cellular senescence. ACS is elicited by a variety of chemotherapeutic agents in the p53-null, p16-deficient human non-smatl cell H1299 carcinoma cells. After 10 to 21 days, infrequent ACS cells (1 in 10(6)) can bypass replicative arrest and reenter cell cycle. These cells express senescence markers and resemble the parental cells in their transcription profile. We show that these escaped H1299 cells overexpress the cyclin-dependent kinase Cdc2/Cdkl. The escape from ACS can be disrupted by Cdc2/Cdkl kinase inhibitors or by knockdown of Cdc2/Cdkl with small interfering RNA and can be promoted by expression of exogenous Cdc2/Cdkl. We also present evidence that ACS occurs in vivo in human lung cancer following induction chemotherapy. Viable tumors following chemotherapy also overexpress Cdc2/Cdkl. We propose that ACS is a mechanism of in vivo tumor response and that mechanisms aberrantly up-regulate Cdc2/Cdkl promotes escape from the senescence pathway may be involved in a subset of tumors and likely accounts for tumor recurrence/progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据