p38MAPK activation is involved in androgen-independent proliferation of human prostate cancer cells by regulating IL-6 secretion.
Increased levels of serum interleukin-6 (IL-6) are frequently observed in patients with advanced, hormone-refractory prostate cancer. However, the precise mechanism of IL-6 regulation is still largely unknown. Since prostate cancer gradually progresses to an androgen-independent state despite the stress caused by various therapeutic agents, we hypothesized the stress-activated protein kinases (SAPKs) involvement in androgen-independent growth or IL-6 secretion of prostate cancer cells. Using PC-3 and DU145 human prostate cancer cells, we analyzed the role of SAPKs in IL-6 mediated cell growth and found that the p38MAPK and JNK are involved in androgen-independent cancer cell growth. Furthermore, IL-6 secretion by PC-3 and DU145 cells was significantly suppressed by SAPKs inhibitor, especially by p38MAPK inhibitor SB203580, but not by JNK inhibitor SP600125 nor by MEK inhibitor, PD98059. These results raised the possibility that the IL-6 mediated androgen-independent proliferation of PC-3 and DU145 cells is regulated at least partly via SAPKs signaling pathway especially through p38MAPK activation.
Shida
Yohei
Y
Division of Nephro-Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Igawa
Tsukasa
T
Hakariya
Tomoaki
T
Sakai
Hideki
H
Kanetake
Hiroshi
H
D000728:Androgens / Q000502:physiology; D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D012312:Ritodrine; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000728:Androgens; D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D015850:Interleukin-6; D011725:Pyridines; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D012312:Ritodrine; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one