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 language||English (US)|
|Number of pages||6|
|Journal||International Journal of Cancer|
|State||Published - Oct 8 1998|
ASJC Scopus subject areas
- Cancer Research