Activation of MAP kinase cascade induced by human pancreatic phospholipase A2 in a human pancreatic cancer cell line.
We have found that the growth of human pancreatic cancer cells MIAPaCa-2, induced by human pancreatic phospholipase A2 group I (hPLA2-I), is mediated via its specific receptor but not via its catalytic property. The present study showed that the activation of mitogen-activated protein kinase (MAPK) cascade in MIAPaCa-2 cells is induced by hPLA2-I: this digestive enzyme induced phosphorylation of MEK1/2, p44/42 MAPK and ATF-2, and the phosphorylation in the MAPK cascade was inhibited after the cells were pre-incubated with a selective inhibitor of MEK, PD98059. In addition, this inhibitor dose-dependently blocked the hPLA2-I-induced MIAPaCa-2 proliferation, suggesting that activation of the MAPK cascade is essential for the hPLA2-I-induced MIAPaCa-2 proliferation.
Kinoshita
E
E
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Minami-ku, Japan.
Handa
N
N
Hanada
K
K
Kajiyama
G
G
Sugiyama
M
M
D051698:Activating Transcription Factor 2; D016718:Arachidonic Acid / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D016718:Arachidonic Acid; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D010741:Phospholipases A; D054467:Phospholipases A2