Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B.
The activation of mitogen-activated protein kinase (MAP kinase) and the regulation of cyclooxygenase 2 (COX-2) were investigated in the human endometrial adenocarcinoma cell line HEC-1B by treatment with platelet-activating factor (PAF) and hCG. Pre-treatment of the cells with both oestradiol and medroxyprogesterone acetate was required for MAP kinase activation and COX-2 expression to respond to PAF and hCG. PAF-induced MAP kinase activation was sensitive to MAP kinase kinase (MEK) inhibitor, PD098059, and phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. In contrast, hCG-induced MAP kinase activation was sensitive to PD098059 and protein kinase A inhibitor, H-89, but not to wortmannin. PAF-induced COX-2 expression was insensitive to PD098059 but sensitive to wortmannin, whereas hCG-induced COX-2 expression was sensitive to PD098059 and H-89 but insensitive to wortmannin. 8-(4-chlorophenylthio)-cAMP, a potent cAMP analogue, induced activation of MAP kinase and expression of COX-2. These results indicate that MAP kinase is activated with PAF and hCG in HEC-1B cells. In addition, COX-2 expression is stimulated through the MAP kinase activation pathway with hCG and the wortmannin sensitive pathway with PAF in HEC-1B cells. These results also imply that protein kinase A remains upstream of hCG-induced activation of MAP kinase in HEC-1B cells.
Munir
I
I
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
Fukunaga
K
K
Miyazaki
K
K
Okamura
H
H
Miyamoto
E
E
D000230:Adenocarcinoma; D000730:Androstadienes / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D051546:Cyclooxygenase 2; D016889:Endometrial Neoplasms; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D007546:Isoquinolines; D008565:Membrane Proteins; D008934:Mitogens; D010972:Platelet Activating Factor; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin