[ERK1/2 and p38 kinases are important regulators in P2Y receptor-mediated prostate cancer invasion].
OBJECTIVE
To explore whether ERK1/2 and p38 pathways mediate P2Y receptor-induced prostate cancer invasion.


METHODS
The two subclones from the PC-3 human prostate carcinoma cell line: 1E8 (highly metastatic) and 2B4 (non-metastatic), were cultured and transfected with the plasmid pcDNA3-KA-MEK1 containing the dominant negative mutant of MEK1 (KA-MEK1) and wild type MKP-5 (a dual-specificity phosphatase of p38). P2Y receptor-activated ERK1/2 and p38 kinases were detected using phospho-specific antibodies directed against the dually phosphorylated active forms of these kinases by Western blotting. P2Y receptor agonists ATP and P2Y receptor antagonist suramin were used respectively to observe their effects on the activity of ERK1/2. The roles ERK1/2 and p38 pathways play in P2Y receptor-induced in vitro invasion were detected by in vitro invasion assay. The cells were pre-treated with ATP, SB203580, a p38 inhibitor, and PD98059, a blocker of ERK1/2 pathway, respectively.


RESULTS
ATP activated ERK1/2 and p38 kinase time-dependently. Suramin significantly inhibited the activation of ERK1/2 and p38 kinase by ATP. ATP stimulated prostate cancer cell invasion. The stimulated cancer cell invasion was significantly inhibited by pretreatment of the cells with PD98059 or SB203580. Transfected of 1E8 cells with KA-MEK1 or up-regulation of MKP-5 both, while inhibiting phosphorylation of ERK1/2 or p38, significantly reduced the invasion of prostate cancer cells in vitro.


CONCLUSIONS
P2Y receptor-induced prostate cancer cell invasion is mainly regulated through ERK1/2 and p38 pathways.
Chen
Ling
L
Department of Pathology, Peking University Health Science Center, Beijing 100083, China.
He
Hui-Ying
HY
Li
Hong-Mei
HM
You
Jiang-Feng
JF
Heng
Wan-Jie
WJ
Li
Yan
Y
Fang
Wei-Gang
WG
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D018048:Receptors, Purinergic P2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one