Glypican-1 antisense transfection modulates TGF-β-dependent signaling in Colo-357 pancreatic cancer cells

Junsheng Li, Jörg Kleeff, Hany Kayed, Klaus Felix, Roland Penzel, Markus W. Büchler, Murray Korc, Helmut Friess

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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-β 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-β1 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-β1 induced cell growth inhibition, Smad2 phosphorylation, and PAI-1 promoter activity. There was, however, no significant difference in TGF-β1 induced p21 expression and Smad2 nuclear translocation. In conclusion, glypican-1 is required for efficient TGF-β1 signaling in pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)1148-1155
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume320
Issue number4
DOIs
StatePublished - Aug 6 2004
Externally publishedYes

Fingerprint

Glypicans
Pancreatic Neoplasms
Transfection
Cells
Cell growth
Phosphorylation
Plasminogen Activator Inhibitor 1
Assays
Growth
Fibroblast Growth Factor Receptors
Heparan Sulfate Proteoglycans
Fibroblast Growth Factor 2
Luciferases
Agar
Immunoblotting
Down-Regulation

Keywords

  • Glypican
  • Heparansulfate
  • Pancreatic cancer
  • Proteoglycans
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Glypican-1 antisense transfection modulates TGF-β-dependent signaling in Colo-357 pancreatic cancer cells. / Li, Junsheng; Kleeff, Jörg; Kayed, Hany; Felix, Klaus; Penzel, Roland; Büchler, Markus W.; Korc, Murray; Friess, Helmut.

In: Biochemical and Biophysical Research Communications, Vol. 320, No. 4, 06.08.2004, p. 1148-1155.

Research output: Contribution to journalArticle

Li, Junsheng ; Kleeff, Jörg ; Kayed, Hany ; Felix, Klaus ; Penzel, Roland ; Büchler, Markus W. ; Korc, Murray ; Friess, Helmut. / Glypican-1 antisense transfection modulates TGF-β-dependent signaling in Colo-357 pancreatic cancer cells. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 320, No. 4. pp. 1148-1155.
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