Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells.

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Research Abstract Details 

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Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Abstract Text:

S A Byron,K B Horwitz,J K Richer,C A Lange,X Zhang,D Yee,

Activation of the type I insulin-like growth factor receptor (IGF-IR) regulates several aspects of the malignant phenotype, including cancer cell proliferation and metastasis. Phosphorylation of adaptor proteins downstream of IGF-IR may couple IGF action to specific cancer phenotypes. In this study, we sought to determine if insulin receptor substrate-1 and -2 (IRS-1 and -2) mediate distinct biological effects in breast cancer cells. Insulin receptor substrate-1 and IRS-2 were expressed in T47D-YA breast cancer cells, which lack IRS-1 and -2 expression, yet retain functional IGF-IR. In the absence of IRS-1 and -2 expression, IGF-IR activation was unable to stimulate proliferation or motility in T47D-YA cells. Expression of IRS-1 resulted in IGF-I-stimulated proliferation, but did not affect motility. In contrast, expression of IRS-2 enhanced IGF-I-stimulated motility, but did not stimulate proliferation. The alphaIR-3, an inhibitor of the IGF-IR, was unable to affect these IGF-stimulated phenotypes unless IRS-1 or -2 was expressed. Thus, IGF-IR alone is unable to regulate important breast cancer cell phenotypes. In these cells, IRS proteins are required for and mediate distinct aspects of IGF-IR-stimulated behaviour. As multiple agents targeting the IGF-IR are currently in early clinical trials, IRS expression should be considered as a potential biomarker for IGF-IR responsiveness.

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Publishing Authors By Initials

SA Byron,KB Horwitz,JK Richer,CA Lange,X Zhang,D Yee,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: British journal of cancer

VOLUME: 95

Page Numbers: 1220-8

Journal Abbreviation: Br. J. Cancer

ISSN: 0007-0920

DAY: 17

MONTH: 10

YEAR: 2006

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370635

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: physiology

Chemical & Substance for Abstract: Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Information

Substance Name: Receptor, IGF Type 1

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells.

AFFILIATION: Department of Pharmacology, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.

Country: England

AGENCY: United States NCI

GRANT: P30 CA77398

ACRONYM: CA

MEDLINETA: Br J Cancer

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