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

Mei Ling Chen, Pei Zhang Xu, Xiao Ding Peng, William S. Chen, Grace Guzman, Ximing Yang, Antonio Di Cristofano, Pier Paolo Pandolfi, Nissim Hay

Research output: Contribution to journalArticle

205 Citations (Scopus)

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 highgrade prostate intraepithelial neoplasia (PIN) and endometrial carcinoma. These results have significant implications for cancer therapy.

Original languageEnglish (US)
Pages (from-to)1569-1574
Number of pages6
JournalGenes and Development
Volume20
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

Fingerprint

Neoplasms
Prostate
Intestinal Polyps
Adrenal Medulla
Carcinoma in Situ
Endometrial Neoplasms
Endometrium
Thyroid Gland
Carcinogenesis
Therapeutics

Keywords

  • Cancer therapy
  • Endometrium carcinoma
  • Intestinal polyps
  • PIN
  • Thyroid and adrenal tumors

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Chen, M. L., Xu, P. Z., Peng, X. D., Chen, W. S., Guzman, G., Yang, X., ... Hay, N. (2006). The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Genes and Development, 20(12), 1569-1574. https://doi.org/10.1101/gad.1395006

The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. / Chen, Mei Ling; Xu, Pei Zhang; Peng, Xiao Ding; Chen, William S.; Guzman, Grace; Yang, Ximing; Di Cristofano, Antonio; Pandolfi, Pier Paolo; Hay, Nissim.

In: Genes and Development, Vol. 20, No. 12, 15.06.2006, p. 1569-1574.

Research output: Contribution to journalArticle

Chen, ML, Xu, PZ, Peng, XD, Chen, WS, Guzman, G, Yang, X, Di Cristofano, A, Pandolfi, PP & Hay, N 2006, 'The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice', Genes and Development, vol. 20, no. 12, pp. 1569-1574. https://doi.org/10.1101/gad.1395006
Chen ML, Xu PZ, Peng XD, Chen WS, Guzman G, Yang X et al. The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Genes and Development. 2006 Jun 15;20(12):1569-1574. https://doi.org/10.1101/gad.1395006
Chen, Mei Ling ; Xu, Pei Zhang ; Peng, Xiao Ding ; Chen, William S. ; Guzman, Grace ; Yang, Ximing ; Di Cristofano, Antonio ; Pandolfi, Pier Paolo ; Hay, Nissim. / The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. In: Genes and Development. 2006 ; Vol. 20, No. 12. pp. 1569-1574.
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