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

Content Provider	Semantic Scholar
Author	Lesche, Ralf Li, Dong Min Liliental, J. Zhang, Hao Gao, Jinming Gavrilova, Nadia Mueller, Bradford J. Liu, Xu-Hui
Copyright Year	1999
Abstract	To investigate the molecular basis of PTEN-mediated tumor suppression, we introduced a null mutation into the mouse Pten gene by homologous recombination in embryonic stem (ES) cells. Pten-/- ES cells exhibited an increased growth rate and proliferated even in the absence of serum. ES cells lacking PTEN function also displayed advanced entry into S phase. This accelerated G1/S transition was accompanied by down-regulation of p27(KIP1), a major inhibitor for G1 cyclin-dependent kinases. Inactivation of PTEN in ES cells and in embryonic fibroblasts resulted in elevated levels of phosphatidylinositol 3,4,5,-trisphosphate, a product of phosphatidylinositol 3 kinase. Consequently, PTEN deficiency led to dosage-dependent increases in phosphorylation and activation of Akt/protein kinase B, a well-characterized target of the phosphatidylinositol 3 kinase signaling pathway. Akt activation increased Bad phosphorylation and promoted Pten-/- cell survival. Our studies suggest that PTEN regulates the phosphatidylinositol 3,4, 5,-trisphosphate and Akt signaling pathway and consequently modulates two critical cellular processes: cell cycle progression and cell survival.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.96.11.6199
Alternate Webpage(s)	http://labs.pharmacology.ucla.edu/hwulab/sun%20pnas%2099.pdf
PubMed reference number	10339565
Alternate Webpage(s)	https://doi.org/10.1073/pnas.96.11.6199
Journal	Medline
Volume Number	96
Issue Number	11
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article