The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/− mice

ML Chen, PZ Xu, X Peng, WS Chen… - Genes & …, 2006 - genesdev.cshlp.org
ML Chen, PZ Xu, X Peng, WS Chen, G Guzman, X Yang, A Di Cristofano, PP Pandolfi
Genes & development, 2006genesdev.cshlp.org
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 …
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.
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