Activation of MAP kinase cascade induced by human pancreatic phospholipase A2 in a human pancreatic cancer cell line

FEBS Letters

Sugiyama, Masanori²  Handa, Noriko²  Hanada, Keiji¹  Kajiyama, Goro¹  Kinoshita, Eiji² 

[1] First Department of Internal Medicine, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734 Japan;Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734, Japan

关键词: Arachidonic acid metabolism;    Human pancreatic phospholipase A2;    MAP kinase;    MIAPaCa-2;    Proliferation;    AA;    arachidonic acid;    DMEM;    Dulbecco's modified Eagle's medium;    FBS;    fetal bovine serum;    h;    human;    MAPK;    mitogen-activated protein kinase;    MEK;    MAPK or ERK kinase;    NDGA;    nordihydroguaiaretic acid;    PAGE;    polyacrylamide gel electrophoresis;    PLA2-I;    group I of phospholipase A2;    PLA2-II;    group II of phospholipase A2;    SDS;    sodium dodecyl sulfate;   

DOI  :  10.1016/S0014-5793(97)00373-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown