Glypican-1 antisense transfection modulates TGF-beta-dependent signaling in Colo-357 pancreatic cancer cells.
The heparan sulfate proteoglycan glypican-1 is essential as a co-receptor for heparin binding growth factors, such as HB-EGF and FGF-2, in pancreatic cancer cells. In the present study, the role of glypican-1 in the regulation of TGF-beta signaling was investigated. Colo-357 pancreatic cancer cells were stably transfected with a full-length glypican-1 antisense construct. Cell growth was determined by MTT and soft agar assays. TGF-beta1 induced p21 expression and Smad2 phosphorylation were analyzed by immunoblotting. PAI-1 promoter activity was determined by luciferase assays. Down-regulation of glypican-1 expression by stable transfection of a full-length glypican-1 antisense construct resulted in decreased anchorage-dependent and -independent cell growth in Colo-357 pancreatic cancer cells and attenuated TGF-beta1 induced cell growth inhibition, Smad2 phosphorylation, and PAI-1 promoter activity. There was, however, no significant difference in TGF-beta1 induced p21 expression and Smad2 nuclear translocation. In conclusion, glypican-1 is required for efficient TGF-beta1 signaling in pancreatic cancer cells.
Li
Junsheng
J
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Kleeff
Jörg
J
Kayed
Hany
H
Felix
Klaus
K
Penzel
Roland
R
Büchler
Markus W
MW
Korc
Murray
M
Friess
Helmut
H
D002455:Cell Division; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016373:DNA, Antisense; D019812:Heparan Sulfate Proteoglycans; D016212:Transforming Growth Factor beta