Ligand induced upregulation of the type II transforming growth factor (TGF-β) receptor enhances TGF-β responsiveness in COLO-357 cells

Jörg Kleeff, Stefan Wildi, Helmut Friess, Murray Korc

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The effects of transforming growth factor (TGF)β1 on type I and type II TGF-β receptor (TβRI and TβRII) expression were examined in five pancreatic cancer cell lines. In contrast to its actions in COLO-357, a TGF- β-sensitive pancreatic cancer cell line, TGF-β1 did not significantly alter TGF-β receptor expression in either the TGF-β-sensitive BXPC-3 and PANC-1 cells or in the TGF-β-resistant CAPAN-1 and T3M4 cells. Neutralizing anti- TβRII antibodies blocked TGF-β1-dependent signaling in COLO-357 cells but exhibited an attenuated effect in COLO-357 cells preincubated with TGF-β1 for 48 h. Basal TβRII expression levels were comparable in all five cell lines examined. In contrast, COLO-357 cells and BX-PC-3 cells expressed relatively high basal levels of TβRI. However, COLO-357 cells harbored a normal Smad4 gene, whereas BX-PC-3 cells exhibited a complete deletion of this gene. We conclude that the TGF-β1-induced TβRII upregulation serves to enhance TGF-β1 responsiveness in COLO-357 cells, and that this upregulation requires the presence of adequate levels of TβRI and TβRII, and a functional Smad4 gene product. Our findings also indicate that TGF-β1 may inhibit pancreatic cancer cell growth via a Smad4-independent pathway.

Original languageEnglish (US)
Pages (from-to)364-370
Number of pages7
JournalPancreas
Volume18
Issue number4
StatePublished - May 1999
Externally publishedYes

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Up-Regulation
Ligands
Pancreatic Neoplasms
Cell Line
Gene Deletion
Neutralizing Antibodies
Genes
Anti-Idiotypic Antibodies

Keywords

  • Pancreatic cancer
  • Smad4
  • TGF-β
  • TGF-β-receptor regulation

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Ligand induced upregulation of the type II transforming growth factor (TGF-β) receptor enhances TGF-β responsiveness in COLO-357 cells. / Kleeff, Jörg; Wildi, Stefan; Friess, Helmut; Korc, Murray.

In: Pancreas, Vol. 18, No. 4, 05.1999, p. 364-370.

Research output: Contribution to journalArticle

Kleeff, Jörg ; Wildi, Stefan ; Friess, Helmut ; Korc, Murray. / Ligand induced upregulation of the type II transforming growth factor (TGF-β) receptor enhances TGF-β responsiveness in COLO-357 cells. In: Pancreas. 1999 ; Vol. 18, No. 4. pp. 364-370.
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