ERK1/2 and p38 pathways are required for P2Y receptor-mediated prostate cancer invasion.
The G protein-coupled P2Y purinoceptors have wide physiological functions, but their role(s) in tumor progression remain unclear. Here, we report that stimulation of P2Y receptors enhances prostate cancer cell invasion in two human prostate carcinoma cell lines, which is mediated by ERK1/2 and p38 signaling pathways. P2Y agonists stimulated prostate cancer cell invasion, and increased the activities of ERK1/2 and p38 protein kinases. The stimulated cancer cell invasion was inhibited by the presence of MEK1 inhibitor PD98059 or p38 inhibitor SB203580. Expression of dominant-negative mutant of MEK1 (KA-MEK1), or up-regulation of MKP-5 (a dual-specificity phosphatase of p38), both reduced the invasion of cultured prostate cancer cells. These results suggest that P2Y receptors and their down-stream ERK1/2 and p38 protein kinases are important regulators promoting prostate cancer invasion.
Department of Pathology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Ling
L
Chen
Hui-ying
HY
He
Hong-mei
HM
Li
Jie
J
Zheng
Wan-jie
WJ
Heng
Jiang-feng
JF
You
Wei-gang
WG
Fang
D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018048:Receptors, Purinergic P2; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases