Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells.
To elucidate possible mechanisms of phorbol 12-myristate 13-acetate (PMA) induced in vitro invasiveness of glioblastoma cells, we examined expression levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using Western blotting and gelatin zymography assay, and found that PMA induced the secretion of MMP-9, activated MMP-2 proenzyme to fully active form of 59 kDa, down-regulated the TIMP-1 and TIMP-2 secretion, and increased MT1-MMP on the cell surface. However, PKC inhibitor Go 6983 reversed all of these effects brought about by PMA. We, therefore, conclude the activation of PKC by PMA in these cells plays a critical role in the regulation of MMPs/TIMPs system, which has a major role in tumor invasion and metastasis.
Park
M J
MJ
Laboratory of Cell Biology, Korea Cancer Center Hospital, 215-4 Gongneung-dong, Nowon-ku, 139-240, Seoul, South Korea.
Park
I C
IC
Hur
J H
JH
Rhee
C H
CH
Choe
T B
TB
Yi
D H
DH
Hong
S I
SI
Lee
S H
SH
D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010703:Phorbol Esters / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D010703:Phorbol Esters; D019714:Tissue Inhibitor of Metalloproteinases; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D011493:Protein Kinase C; D020782:Matrix Metalloproteinases; D013755:Tetradecanoylphorbol Acetate