Prostate cancer is one of the most common cancers among men. Recent studies demonstrated that PI3K signaling is an important intracellular mediator which is involved in multiple cellular functions including proliferation, differentiation, anti-apoptosis, tumorigenesis, and angiogenesis. In the present study, we demonstrate that the inhibition of PI3K activity by LY294002, inhibited prostate cancer cell proliferation and induced the G1 cell cycle arrest. This effect was accompanied by the decreased expression of G 1-associated proteins including cyclin D1, CDK4, and Rb phosphorylation at Ser780, Ser795, and Ser807/811, whereas expression of CDK6 and β-actin was not affected by LY294002. The expression of cyclin kinase inhibitor, p21CIP1/WAF1, was induced by LY294002, while levels of p16INK4 were decreased in the same experiment. The inhibition of PI3K activity also inhibited the phosphorylation and p70S6K, but not MAPK. PI3K regulates cell cycle through AKT, mTOR to p70S6K. The mTOR inhibitor rapamycin has similar inhibitory effects on G1 cell cycle progression and expression of cyclin D1, CDK4, and Rb phosphorylation. These results suggest that PI3K mediates G1 cell cycle progression and cyclin expression through the activation of AKT/mTOR/p70S6K signaling pathway in the prostate cancer cells.
|Number of pages||9|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Oct 31 2003|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology