Short telomeres limit tumor progression in vivo by inducing senescence
Short telomeres limit tumor progression in vivo by inducing senescence
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DOI：
10.1016/j.ccr.2007.02.026
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发表时间：
2007-05-01
期刊：
影响因子：
50.3
通讯作者：
Greider, Carol W.
中科院分区：
文献类型：
--
作者：
Feldser, David M.;Greider, Carol W.
端粒维持对于癌症进展至关重要。为了研究短端粒诱导的肿瘤抑制机制，我们将端粒酶RNA组分mTR（-/-）缺陷的小鼠与E mu-myc转基因小鼠（一种已建立的伯基特淋巴瘤模型）杂交。短端粒抑制E mu-myc转基因动物的肿瘤形成。Bcl 2的表达阻断了肿瘤细胞的凋亡，但令人惊讶的是，端粒短的小鼠仍然对肿瘤形成有抵抗力。细胞衰老标记物的染色显示，肿瘤前细胞响应于短端粒而诱导衰老。p53的缺失废除了短端粒反应。这项研究提供了体内证据的存在p53介导的衰老机制，在短端粒，抑制肿瘤发生。
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.