PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt protein kinase B signaling pathway

Citation
H. Sun et al., PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt protein kinase B signaling pathway, P NAS US, 96(11), 1999, pp. 6199-6204
Citations number
34
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
11
Year of publication
1999
Pages
6199 - 6204
Database
ISI
SICI code
0027-8424(19990525)96:11<6199:PMCCPA>2.0.ZU;2-R
Abstract
To investigate the molecular basis of PTEN-mediated tumor suppression, we i ntroduced a null mutation into the mouse Pten gene by homologous recombinat ion in embryonic stem (ES) cells. Pten(-/-) ES cells exhibited an increased growth rate and proliferated even in the absence of serum. ES cells lackin g PTEN function also displayed advanced entry into S phase. This accelerate d G(1)/S transition was accompanied by down-regulation of p27(KIP1), a majo r inhibitor for G(1) cyclin-dependent kinases. Inactivation of PTEN in ES c ells and in embryonic fibroblasts resulted in elevated levels of phosphatid ylinositol 3,4,5,-trisphosphate, a product of phosphatidylinositol 3 kinase . Consequently, PTEN deficiency led to dosage-dependent increases in phosph orylation and activation of Akt/protein kinase B, a well-characterized targ et of the phosphatidylinositol 3 kinase signaling pathway. Akt activation i ncreased Bad phosphorylation and promoted Pten(-/-) cell survival. Our stud ies suggest that PTEN regulates the phosphatidylinositol 3,4,5,-trisphospha te and Akt signaling pathway and consequently modulates two critical cellul ar processes: cell cycle progression and cell survival.