Short telomeres limit tumor progression in vivo by inducing senescence

被引：253

作者：

Feldser, David M.

Greider, Carol W. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Program Human Genet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

来源：

CANCER CELL | 2007年 / 11卷 / 05期

关键词：

D O I：

10.1016/j.ccr.2007.02.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Telomere maintenance is critical for cancer progression. To examine mechanisms of tumor suppression induced by short telomeres, we crossed mice deficient for the RNA component of telomerase, mTR(-/-), with E mu-myc transgenic mice, an established model of Burkitt's lymphoma. Short telomeres suppressed tumor formation in E mu-myc transgenic animals. Expression of Bcl2 blocked apoptosis in tumor cells, but surprisingly, mice with short telomeres were still resistant to tumor formation. Staining for markers of cellular senescence showed that pretumor cells induced senescence in response to short telomeres. Loss of p53 abrogated the short telomere response. This study provides in vivo evidence for the existence of a p53-mediated senescence mechanism in response to short telomeres that suppresses tumorigenesis.

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页码：461 / 469

页数：9

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