TY - JOUR
T1 - Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity
AU - Ito, Hiromichi
AU - Duxbury, Mark
AU - Zinner, Michael J.
AU - Ashley, Stanley W.
AU - Whang, Edward E.
PY - 2004/9/1
Y1 - 2004/9/1
N2 - Overexpression of the facilitative glucose transporter-1 (GLUT-1) has been observed for a wide range of human cancers, with the degree of overexpression generally being inversely correlated with prognosis. We tested the effects of modulating GLUT-1 expression on pancreatic cancer cellular invasiveness.GLUT-1 expression in MIAPaCa-2, PANC-1, BXPC-3, and CAPAN-2 cells was assayed using Western blotting. Cells were stably transfected with a GLUT-1 expression vector or a GLUT-1 RNA interference vector to alter GLUT-1 expression. Matrix metalloproteinase-2 (MMP-2) activity and expression were assayed using zymography and Western blotting, respectively. In vitro cellular invasiveness was assayed using Matrigel Boyden chambers, and in vivo metastatic potential was assessed using a nude mouse xenograft model.Variable baseline GLUT-1 expression levels were detected among the cell lines. Forced overexpression of GLUT-1 induced increases in MMP-2 expression and activity and in cellular invasiveness. GLUT-1 silencing induced reductions in MMP-2 expression and activity, cellular invasiveness, and metastatic potential in vivo.GLUT-1 promotes pancreatic cellular invasiveness. The therapeutic implications of this finding warrant further study.
AB - Overexpression of the facilitative glucose transporter-1 (GLUT-1) has been observed for a wide range of human cancers, with the degree of overexpression generally being inversely correlated with prognosis. We tested the effects of modulating GLUT-1 expression on pancreatic cancer cellular invasiveness.GLUT-1 expression in MIAPaCa-2, PANC-1, BXPC-3, and CAPAN-2 cells was assayed using Western blotting. Cells were stably transfected with a GLUT-1 expression vector or a GLUT-1 RNA interference vector to alter GLUT-1 expression. Matrix metalloproteinase-2 (MMP-2) activity and expression were assayed using zymography and Western blotting, respectively. In vitro cellular invasiveness was assayed using Matrigel Boyden chambers, and in vivo metastatic potential was assessed using a nude mouse xenograft model.Variable baseline GLUT-1 expression levels were detected among the cell lines. Forced overexpression of GLUT-1 induced increases in MMP-2 expression and activity and in cellular invasiveness. GLUT-1 silencing induced reductions in MMP-2 expression and activity, cellular invasiveness, and metastatic potential in vivo.GLUT-1 promotes pancreatic cellular invasiveness. The therapeutic implications of this finding warrant further study.
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U2 - 10.1016/j.surg.2004.05.032
DO - 10.1016/j.surg.2004.05.032
M3 - Article
C2 - 15349101
AN - SCOPUS:4444302818
VL - 136
SP - 548
EP - 556
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 3
ER -