Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor

Joëlle Dupont, Ana M. Fernandez, Charlotta A. Glackin, Lee J. Helman, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

In this study we investigated the molecular mechanisms whereby insulin-like growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10-8 M) for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In contrast, insulin at physiological concentrations did not stimulate Twist expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Preincubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells, suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of Twist in mouse skeletal muscle, the major site of Twist expression. Finally, using an antisense strategy, we demonstrated that a reduction of 40% in Twist expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells from etoposide-induced apoptosis. Taken together, these results define Twist as an important factor involved in the anti-apoptotic actions of the IGF-1 receptor.

Original languageEnglish (US)
Pages (from-to)26699-26707
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number28
DOIs
StatePublished - Jul 13 2001
Externally publishedYes

Fingerprint

Somatomedin Receptors
Somatomedins
Messenger RNA
Fibroblasts
Mitogen-Activated Protein Kinase Kinases
Etoposide
Mitogen-Activated Protein Kinases
Skeletal Muscle
Insulin
Apoptosis
Gene Expression
Gene expression
Injections
Muscle

ASJC Scopus subject areas

  • Biochemistry

Cite this

Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor. / Dupont, Joëlle; Fernandez, Ana M.; Glackin, Charlotta A.; Helman, Lee J.; LeRoith, Derek.

In: Journal of Biological Chemistry, Vol. 276, No. 28, 13.07.2001, p. 26699-26707.

Research output: Contribution to journalArticle

Dupont, Joëlle ; Fernandez, Ana M. ; Glackin, Charlotta A. ; Helman, Lee J. ; LeRoith, Derek. / Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 28. pp. 26699-26707.
@article{545ebb80c33b42c78e33e7859a6c14ef,
title = "Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor",
abstract = "In this study we investigated the molecular mechanisms whereby insulin-like growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10-8 M) for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In contrast, insulin at physiological concentrations did not stimulate Twist expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Preincubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells, suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of Twist in mouse skeletal muscle, the major site of Twist expression. Finally, using an antisense strategy, we demonstrated that a reduction of 40{\%} in Twist expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells from etoposide-induced apoptosis. Taken together, these results define Twist as an important factor involved in the anti-apoptotic actions of the IGF-1 receptor.",
author = "Jo{\"e}lle Dupont and Fernandez, {Ana M.} and Glackin, {Charlotta A.} and Helman, {Lee J.} and Derek LeRoith",
year = "2001",
month = "7",
day = "13",
doi = "10.1074/jbc.M102664200",
language = "English (US)",
volume = "276",
pages = "26699--26707",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "28",

}

TY - JOUR

T1 - Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor

AU - Dupont, Joëlle

AU - Fernandez, Ana M.

AU - Glackin, Charlotta A.

AU - Helman, Lee J.

AU - LeRoith, Derek

PY - 2001/7/13

Y1 - 2001/7/13

N2 - In this study we investigated the molecular mechanisms whereby insulin-like growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10-8 M) for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In contrast, insulin at physiological concentrations did not stimulate Twist expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Preincubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells, suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of Twist in mouse skeletal muscle, the major site of Twist expression. Finally, using an antisense strategy, we demonstrated that a reduction of 40% in Twist expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells from etoposide-induced apoptosis. Taken together, these results define Twist as an important factor involved in the anti-apoptotic actions of the IGF-1 receptor.

AB - In this study we investigated the molecular mechanisms whereby insulin-like growth factor 1 (IGF-1) induced Twist gene expression and the role of Twist in the anti-apoptotic actions of the IGF-1 receptor. In NIH-3T3 fibroblasts overexpressing the human IGF-1 receptor (NWTb3), treatment with IGF-1 (10-8 M) for 1 and 4 h increased the level of Twist mRNA as well as protein by 3-fold. In contrast, insulin at physiological concentrations did not stimulate Twist expression in NIH-3T3 fibroblasts overexpressing the human insulin receptor. The IGF-1 effect was specific for the IGF-1 receptor since, in cells overexpressing a dominant negative IGF-1 receptor, IGF-1 failed to increase Twist expression. Preincubation with the ERK1/2 inhibitor U0126 or expression of a dominant negative MEK-1 abolished the effect of IGF-1 on Twist mRNA expression in NWTb3 cells, suggesting that Twist induction by IGF-1 occurs via the mitogen-activated protein kinase signaling pathway. In vivo, IGF-1 injection increased the mRNA level of Twist in mouse skeletal muscle, the major site of Twist expression. Finally, using an antisense strategy, we demonstrated that a reduction of 40% in Twist expression decreased significantly the ability of IGF-1 to rescue NWTb3 cells from etoposide-induced apoptosis. Taken together, these results define Twist as an important factor involved in the anti-apoptotic actions of the IGF-1 receptor.

UR - http://www.scopus.com/inward/record.url?scp=0035854773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035854773&partnerID=8YFLogxK

U2 - 10.1074/jbc.M102664200

DO - 10.1074/jbc.M102664200

M3 - Article

VL - 276

SP - 26699

EP - 26707

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 28

ER -