Up-regulation of transforming growth factor (TGF)-β receptors by TGF- β1 in COLO-357 cells

Jörg Kleeff, Murray Korc

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Abstract

In the present study we investigated the actions of transforming growth factor (TGF)-β1 on gene induction and cyclin-dependent kinase inhibitors in relation to TGF-β receptor modulation in COLO-357 pancreatic cancer cells. TGF-β1 inhibited the growth of COLO-357 cells in a time- and dose-dependent manner and caused a rapid but transient increase in plasminogen activator inhibitor-I and insulin-like growth factor binding protein-3 mRNA levels. TGF-β1 caused a delayed but sustained increase in the protein levels of the cyclin-dependent kinase inhibitors p15(Ink4B), p21(Cip1), and p27(Kip1) and a sustained increase in type I and H TGF-β receptors (TβRI and TβRII) mRNA and protein levels. The protein synthesis inhibitor cycloheximide (10 μg/ml) completely blocked the TGF-β1-mediated increase in TβRI and TβRII expression. Furthermore, a nuclear runoff transcription assay revealed that the increase in receptor mRNA levels was due to newly transcribed RNA. There was a significant increase in TβRI and TβRII mRNA levels in confluent cells in comparison to subconfluent (≤80% confluent) controls, as well as in serum- starved cells when compared with cells incubated in medium containing 10% fetal bovine serum. COLO-357 cells expressed a normal SMAD4 gene as determined by Northern blot analysis and sequencing. These results indicate that TGF-β1 modulates a variety of functions in COLO-357 cells and up- regulates TGF-β receptor expression via a transcriptional mechanism, which has the potential to maximize TGF-β1-dependent antiproliferative responses.

Original languageEnglish (US)
Pages (from-to)7495-7500
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
StatePublished - Mar 27 1998

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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