[Activation of p38 and c-Jun NH2-terminal kinase mitogen-activated protein kinases in human prostate carcinoma cell lines with different metastatic potentials].
OBJECTIVE
To investigate the influence of P2 purinoceptor agonist ATP on p38 mitogen-activated protein kinases (MAPK) and JNK (c-Jun NH(2)-terminal kinase) signaling pathway in two human prostate cancer cell sublines (1E8 and 2B4) with different metastasis potentials.


METHODS
Activated p38 and JNK were detected by Western blot with phospho-specific antibodies directed against the dually phosphorylated active forms of p38 or JNK.


RESULTS
Exposure of 1E8 and 2B4 prostate cancer cells to ATP resulted in p38 activation in a concentration- and time-dependent manner. ATP-induced p38 activities were higher in metastatic 1E8 cells when compared with nonmetastatic 2B4 cells. JNK signaling pathway was not activated by ATP. An MEK inhibitor PD 98059 failed to inhibit ATP-induced p38 activation, while p38 inhibitor SB 203580 and P2 purinoceptor antagonist suramin effectively inhibited activation of p38, the inhibition rate being 1E8 83% and 79%, 2B4 81% and 69%. The response of ATP-stimulated p38 to G-protein modulator pertussis toxin in 1E8 and 2B4 cells was not obvious.


CONCLUSIONS
p38 but not JNK signaling pathway can be activated by P2 purinoceptor agonist ATP. Differences of p38 activation by ATP are noted between metastatic 1E8 cells and non-metastatic 2B4 cells. These results provide instructive clues to cancer malignant growth and metastasis research.
Li
H
H
Department of Pathology, Health Science Center, Peking University, Beijing 100083, China.
Fang
W
W
He
C
C
You
J
J
Heng
W
W
Zheng
J
J
Wu
B
B
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013498:Suramin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines; D013498:Suramin; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580