The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice.
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.
Chen
Mei-Ling
ML
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Xu
Pei-Zhang
PZ
Peng
Xiao-ding
XD
Chen
William S
WS
Guzman
Grace
G
Yang
Ximing
X
Di Cristofano
Antonio
A
Pandolfi
Pier Paolo
PP
Hay
Nissim
N
D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D006579:Heterozygote; D007417:Intestinal Polyps / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency* / Q000235:genetics; D019310:Pseudolymphoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology
D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase