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PMID: 11997518 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis.

Molecular and cellular biology ·Vol. 22 ·No. 11 ·2002-06-00 ·Pages 3842-51

Stiles B, Gilman V, Khanzenzon N, Lesche R, Li A, Qiao R, Liu X, Wu H

Abstract

PTEN is mutated at high frequency in many primary human cancers and several familial cancer predisposition disorders. Activation of AKT is a common event in tumors in which the PTEN gene has been inactivated. We previously showed that deletion of the murine Pten gene in embryonic stem (ES) cells led to increased phosphatidylinositol triphosphate (PIP(3)) accumulation, enhanced entry into S phase, and better cell survival. Since PIP(3) controls multiple signaling molecules, it was not clear to what degree the observed phenotypes were due to deregulated AKT activity. In this study, we mutated Akt-1 in Pten(-/-) ES cells to directly assess the role of AKT-1 in PTEN-controlled cellular processes, such as cell proliferation, cell survival, and tumorigenesis in nude mice. We showed that AKT-1 is one of the major downstream effectors of PTEN in ES cells and that activation of AKT-1 is required for both the cell survival and cell proliferation phenotypes observed in Pten(-/-) ES cells. Deletion of Akt-1 partially reverses the aggressive growth of Pten(-/-) ES cells in vivo, suggesting that AKT-1 plays an essential role in PTEN-controlled tumorigenesis.

MeSH Terms
Animals Cell Division Cell Line Cell Survival Enzyme Activation Gene Targeting Humans Mice Mice, Knockout Mice, Nude Mitosis Mutation Neoplasms, Experimental/enzymology,etiology,genetics,pathology PTEN Phosphohydrolase Phenotype Phosphoric Monoester Hydrolases/deficiency,genetics,metabolism Protein Serine-Threonine Kinases/deficiency,genetics,metabolism Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Tumor Suppressor Proteins/deficiency,genetics,metabolism
Chemicals
Proto-Oncogene Proteins Tumor Suppressor Proteins AKT1 protein, human Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Phosphoric Monoester Hydrolases PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Stiles Bangyan
Howard Hughes Medical Institute and Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1735, USA.
Gilman Valeriya
Khanzenzon Natalya
Lesche Ralf
Li Annie
Qiao Rong
Liu Xin
Wu Hong
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40 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.11.3842-3851.2002
Published
2002-06-00
Pages
3842-51
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC133830
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.11.3842-3851.2002 PMC Full Text View journal details
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