Biochemical and Biophysical Research Communications
Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer☆
Section snippets
Materials and methods
Reagents and cell culture. PI3K inhibitor, LY294002, and mTOR/FRAP inhibitor, rapamycin, were purchased from Calbiochem (San Diego, CA). Propidium iodide (PI) was from Molecular Probes (Eugene, OR). The antibodies against p16INK4, p21CIP1/WAF1, CDC25A, CDK4, CDK6, cyclin D1, and β-actin were from Santa Cruz Biotechnology (Santa Cruz, CA); and the antibodies against Rb, Phospho-Rb (Ser780), Phospho-Rb (Ser795), Phospho-Rb (Ser807/811), Phospho-AKT (Ser473), Phospho-p44/42 MAPK, p70S6K,
PI3K regulates G1 cell cycle progression in prostate cancer cells
To elucidate the role of PI3K in regulating the proliferation, DU145 and PC-3 cells were seeded and cultured for 24 h, followed by incubation in the presence or absence of the PI3K inhibitor, LY294002. Total cell numbers were counted 24, 48, and 72 h after the incubation. As shown in Fig. 1A, the number of both OVCAR-3 and A2780-CP70 cells was greatly increased over the period of 72 h culture in the absence of LY294002. The proliferation of DU145 cells was significantly inhibited by LY294002 in a
Discussion
PI3K plays an important role in many cellular functions in response to growth factor. It has been reported that PI3K is required for cellular transformation induced by several viral oncoproteins such as Src and Ab1 [40], [41], [42]. An oncogenic form of PI3K, v-p3k, was discovered recently in avian sarcoma virus 16 and v-p3k is the viral homolog of a gene encoding for PI3K catalytic subunit [7]. Although PI3K signaling has been hypothesized to play an important role in human prostate cancer
References (56)
- et al.
Phosphoinositide 3-kinase and the regulation of cell growth
Biochim. Biophys. Acta
(1996) - et al.
Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase
Blood
(1996) - et al.
Downstream signalling events regulated by phosphatidylinositol 3-kinase activity
Cell Signal
(1998) - et al.
The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB
Exp. Cell Res.
(1999) - et al.
G1 phase arrest by the phosphatidylinositol 3-kinase inhibitor LY 294002 is correlated to up-regulation of p27Kip1 and inhibition of G1 CDKs in choroidal melanoma cells
FEBS Lett.
(1998) - et al.
Purification and characterization of phosphoinositide 3-kinase from rat liver
J. Biol. Chem.
(1990) - et al.
PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells
Cell
(1989) - et al.
FRAP–p70s6K signaling is required for pancreatic cancer cell proliferation
J. Surg. Res.
(2001) - et al.
Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers
Fundam. Appl. Toxicol.
(1997) Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells
Cell
(1992)
Phosphatidylinositol 3′-kinase-independent p70 S6 kinase activation by fibroblast growth factor receptor-1 is important for proliferation but not differentiation of endothelial cells
J. Biol. Chem.
Mitogenic signaling of insulin-like growth factor I in MCF-7 human breast cancer cells requires phosphatidylinositol 3-kinase and is independent of mitogen-activated protein kinase
J. Biol. Chem.
Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cell move through G1
Cell
Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway
J. Biol. Chem.
Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F
Immunity
WAF1, a potential mediator of p53 tumor suppression
Cell
Mice lacking p21CIP1/WAF1 undergo noemal development, but are defective in G1 checkpoint control
Cell
Oncogenic kinase signaling
Nature (Lond.)
Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase
Proc. Natl. Acad. Sci. USA
The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line
J. Exp. Med.
Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase
Science
AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation
Annu. Rev. Biochem.
The akt kinase: molecular determinants of oncogenicity
Proc. Natl. Acad. Sci. USA
Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells
Proc. Natl. Acad. Sci. USA
Inhibition of MG-63 cell proliferation and PDGF-stimulated cellular processes by inhibitors of phosphatidylinositol 3-kinase
J. Cell Biochem.
A tightly associated serine/threonine protein kinase regulates phosphoinositide 3-kinase activity
Mol. Cell. Biol.
PI 3-kinase: structural and functional analysis of intersubunit interactions
EMBO J.
Cited by (0)
- ☆
This work was supported in part by National Institutes of Health NCI Grant RR16440 and American Heart Association Grant 0160166B (to B.H.J.).