Protein kinase C activation by phorbol eater increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells
Mj. Park et al., Protein kinase C activation by phorbol eater increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells, NEUROSCI L, 290(3), 2000, pp. 201-204
To elucidate possible mechanisms of phorbol 12-myristate 13-acetate (PMA) i
nduced 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 secr
etion of MMP-9, activated MMP-2 proenzyme to fully active form of 59 kDa, d
own-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 syste
m, which has a major role in tumor invasion and metastasis. (C) 2000 Elsevi
er Science Ireland Ltd. All rights reserved.