Akt1的缺失足以抑制Pten+/-小鼠的肿瘤发展。
The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice.
作者信息
Chen Mei-Ling, Xu Pei-Zhang, Peng Xiao-ding, Chen William S, Guzman Grace, Yang Ximing, Di Cristofano Antonio, Pandolfi Pier Paolo, Hay Nissim
机构信息
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
出版信息
Genes Dev. 2006 Jun 15;20(12):1569-74. doi: 10.1101/gad.1395006.
Abstract
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.
摘要
肿瘤抑制因子PTEN在人类癌症中常常失活。PTEN的一个主要下游效应分子是Akt，它通过PTEN失活而过度激活。然而，尚不清楚Akt活性降低是否足以抑制由Pten缺陷引发的肿瘤发生。在此我们表明，Akt1缺陷足以显著抑制Pten+/-小鼠的肿瘤发展。Akt1缺陷对子宫内膜和前列腺肿瘤形成有深远影响，这是两种人类癌症类型，其中PTEN经常发生突变，并且还影响甲状腺和肾上腺髓质肿瘤以及肠息肉。即使Akt1单倍体缺陷也足以显著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。
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