Transfection of the type I TGF-β receptor restores TGF-β responsiveness in pancreatic cancer Journal Article
| Authors: | Wagner, M.; Kleeff, J.; Lopez, M. E.; Bockman, I.; Massagué, J.; Korc, M. |
| Article Title: | Transfection of the type I TGF-β receptor restores TGF-β responsiveness in pancreatic cancer |
| 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. |
| Keywords: | signal transduction; human cell; sequence analysis; mutation; dna-binding proteins; dose response; pancreas cancer; pancreatic neoplasms; cell division; transforming growth factor beta; tumor cells, cultured; transfection; genetic transfection; protein-serine-threonine kinases; immunoblotting; reporter gene; transforming growth factor beta1; receptors, transforming growth factor beta; trans-activators; smad4 protein; activin receptors, type i; humans; human; priority journal; article |
| Journal Title: | International Journal of Cancer |
| Volume: | 78 |
| Issue: | 2 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1998-10-05 |
| Start Page: | 255 |
| End Page: | 260 |
| Language: | English |
| DOI: | 10.1002/(sici)1097-0215(19981005)78:2<255::aid-ijc21>3.0.co;2-8 |
| PUBMED: | 9754660 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
