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