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

Jörg Kleeff, Murray Korc

Research output: Contribution to journalArticle

73 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Up-Regulation
Messenger RNA
Cyclin-Dependent Kinase Inhibitor p15
Genes
Plasminogen Inactivators
Insulin-Like Growth Factor Binding Protein 3
Protein Synthesis Inhibitors
Cyclin-Dependent Kinases
Transcription
Cycloheximide
Serum
Runoff
Pancreatic Neoplasms
Northern Blotting
Assays
Proteins
Cells
Modulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Up-regulation of transforming growth factor (TGF)-β receptors by TGF- β1 in COLO-357 cells. / Kleeff, Jörg; Korc, Murray.

In: Journal of Biological Chemistry, Vol. 273, No. 13, 27.03.1998, p. 7495-7500.

Research output: Contribution to journalArticle

@article{636a8f09e6a9411c8bf6413d34c8b3b2,
title = "Up-regulation of transforming growth factor (TGF)-β receptors by TGF- β1 in COLO-357 cells",
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.",
author = "J{\"o}rg Kleeff and Murray Korc",
year = "1998",
month = "3",
day = "27",
doi = "10.1074/jbc.273.13.7495",
language = "English (US)",
volume = "273",
pages = "7495--7500",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - Up-regulation of transforming growth factor (TGF)-β receptors by TGF- β1 in COLO-357 cells

AU - Kleeff, Jörg

AU - Korc, Murray

PY - 1998/3/27

Y1 - 1998/3/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032571373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032571373&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.13.7495

DO - 10.1074/jbc.273.13.7495

M3 - Article

VL - 273

SP - 7495

EP - 7500

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -