The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice
The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice
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DOI：
10.1101/gad.1395006
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发表时间：
2006-06-15
影响因子：
10.5
通讯作者：
Hay, Nissim
中科院分区：
文献类型：
--
作者：
Chen, Mei-Ling;Xu, Pei-Zhang;Hay, Nissim
肿瘤抑制因子PTEN在人类癌症中经常失活。PTEN的一个主要下游效应子是Akt，它通过PTEN失活而被过度激活。然而，目前尚不清楚Akt活性的降低是否足以抑制Pten缺乏引起的肿瘤发生。在这里，我们发现Akt 1的缺陷足以显著抑制Pten（+/-）小鼠的肿瘤发展。Akt 1缺乏对子宫内膜和前列腺肿瘤（其中PTEN经常突变的两种人类癌症）产生深远影响，并且还影响甲状腺和肾上腺髓质肿瘤以及肠息肉。即使Akt 1的单倍缺陷也足以显着减弱高级别前列腺上皮内瘤变（PIN）和子宫内膜癌的发展。这些结果对癌症治疗具有重要意义。
The tumor suppressor PTEN is frequently inactivated in human cancers. A major downstream effector of PTEN is Akt, which is hyperactivated via PTEN inactivation. It is not known, however, whether diminished Akt activity is sufficient to inhibit tumorigenesis initiated by Pten deficiency. Here we showed that the deficiency of Akt1 is sufficient to dramatically inhibit tumor development in Pten(+/-) mice. Akt1 deficiency had a profound effect on endometrium and prostate neoplasia, two types of human cancer, in which PTEN is frequently mutated, and also affected thyroid and adrenal medulla tumors and intestinal polyps. Even haplodeficiency of Akt1 was sufficient to markedly attenuate the development of high-grade prostate intraepithelial neoplasia (PIN) and endometrial carcinoma. These results have significant implications for cancer therapy.