Transfection of the type I TGF-β receptor restores TGF-β responsiveness in pancreatic cancer

Markus Wagner, Jörg Kleeff, Martha E. Lopez, Irene Bockman, Joan Massaqué, Murray Korc

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Transforming growth factor-beta (TGF-β) signaling is initiated following heterodimerization of the type II TGF-β receptor (TβRII) with the type I TGF-β receptor (TβRI). Both receptors are required for TGF-β responsiveness. In the present study, we characterized the actions of TGF- βI in T3M4 human pancreatic cancer cells, which express low levels of TβRI and high levels of TβRII. Cells were transiently transfected with p3TP-Lux, a TGF-β-responsive luciferase reporter gene construct. TGF-βI was without effect in parental T3M4 cells, but caused a time- and dose-dependent increase in luciferase activity in T3M4 cells co-transfected with a TβRI cDNA expression vector. Co-transfection of TβRI with a truncated Smad4 cDNA that is known to block TGF-β-dependent signaling, abrogated the TβRI-induced increase in luciferase activity. Sequencing of the TβRI and the Smad4 genes in T3M4 cells did not reveal any mutations. These findings indicate that one mechanism for TGF-β resistance in pancreatic cancer is due to a quantitative decrease in TβRI expression.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalInternational Journal of Cancer
Volume78
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Transforming Growth Factor beta
Transfection
Luciferases
Transforming Growth Factor beta1
Complementary DNA
Transforming Growth Factor beta Receptors
Reporter Genes
TGF-beta type I receptor
Mutation
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Transfection of the type I TGF-β receptor restores TGF-β responsiveness in pancreatic cancer. / Wagner, Markus; Kleeff, Jörg; Lopez, Martha E.; Bockman, Irene; Massaqué, Joan; Korc, Murray.

In: International Journal of Cancer, Vol. 78, No. 2, 1998, p. 255-260.

Research output: Contribution to journalArticle

Wagner, Markus ; Kleeff, Jörg ; Lopez, Martha E. ; Bockman, Irene ; Massaqué, Joan ; Korc, Murray. / Transfection of the type I TGF-β receptor restores TGF-β responsiveness in pancreatic cancer. In: International Journal of Cancer. 1998 ; Vol. 78, No. 2. pp. 255-260.
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