Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer.

摘要: Background. We have previously reported that the glial cell-derived neurotrophic factor (GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to determine whether GDNF regulates expression and activation matrix metalloproteinase-9 (MMP-9) human cells. Methods. used line MIA PaCa-2. effect on mRNA protein measured by Northern blot, Western blot enzyme-linked immunosorbent assay. MMP proteolytic activity detected gelatin zymography. To which intracellular pathways were involved, we following inhibitors: tyrosine kinase inhibitor Genistein, MEK-1 PD98059 PI3-K Wortmannin. Results. increased MMP-9 PaCa-2 cells a dose-dependent manner. Treatment with enhanced gelatinolytic pro active form MMP-9. Inhibitor experiments showed totally inhibited Genistein partially Wortmannin, whereas had no effect. All three compounds Conclusions. upregulates enzymatic through different signaling These findings suggest modulates activation, may promote invasion. (Surgery 2003;134:293-9.)