ePrints

Increased expression of both insulin receptor substrates 1 and 2 confers increased sensitivity to IGF-1 stimulated cell migration

Lookup NU author(s): Dr Gail de Blaquiere, Dr Felicity May, Professor Bruce Westley

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Insulin-like growth factors (IGFs) are thought to promote tumour progression and metastasis in part by stimulating cell migration. Insulin receptor substrate-1 (IRS-1) and IRS-2 are multisite docking proteins positioned immediately downstream from the type I IGF and insulin receptors IRS-2 but not IRS-1 has been reported to be involved in the migratory response of breast cancer cells to IGFs. The purpose of this investigation was to determine if IRS-1 is involved in, and to assess the contributions of IRS-1 and IRS-2 to, the migratory response of breast cancer cells to IGFs The expression of IRS-1 and IRS-2 varied considerably between ten breast cancer cell lines. Oestrogen increases expression of the type I IGF receptor, IRS-1 and IRS-2 in MCF-7 and ZR-75 cells. Oestrogens may control the sensitivity of breast cancer cells to IGFs by regulating the expression of components of the IGF signal transduction pathway The migratory response to a range of IGF-1 concentrations was measured in MCF-7 and MDA-MB-231 breast cancer cells in which IRS-1 and IRS-2 levels were modulated using a doxycycline-inducible expression system. Induction of both IRS-1 and IRS-2 expression increased the sensitivity of the migratory response to IGF-1 but did not increase the magnitude of the response stimulated at higher concentrations of IGF-1. Knockdown of IRS-1, IRS-2 and the type I IGF receptor in MCF-7 and MDA-MB-2231 cells decreased sensitivity to IGF-1. We conclude that both IRS-1 and IRS-2 control the migratory response of breast cancer cells to IGF-1 and may, therefore, be key molecules in determining breast cancer spread. Endocrine-Related Cancer (2009) 16 635-647

Publication metadata

Author(s): de Blaquière GE, May FEB, Westley BR

Publication type: Article

Publication status: Published

Journal: Endocrine-Related Cancer

Year: 2009

Volume: 16

Issue: 2

Pages: 635-647

Print publication date: 01/06/2009

Online publication date: 04/03/2009

ISSN (print): 1351-0088

ISSN (electronic): 1479-6821

Publisher: Society for Endocrinology

URL: http://dx.doi.org/10.1677/ERC-08-0216

DOI: 10.1677/ERC-08-0216

Altmetrics

Funding

Share