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.

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

PANDOLFI DE RINALDIS, Pier Paolo;
2006-01-01

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.
2006
20
1569
1574
http://dx.doi.org/10.1101/gad.1395006
Adrenal Gland Neoplasms; Animals; Endometrial Neoplasms; Female; Heterozygote; Intestinal Polyps; Male; Mice; Neoplasms; PTEN Phosphohydrolase; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Pseudolymphoma; Thyroid Neoplasms
M. Chen;P. Xu;X. d. Peng;W. S. Chen;G. Guzman;X. Yang;A. D. Cristofano;P. P. Pandolfi;N. Hay
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/63008
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