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Insulin-like Growth Factor-Dependent Proliferation and Survival of Triple-Negative Breast Cancer Cells: Implications for Therapy

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

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

Triple-negative breast cancers have a poor prognosis and are not amenable to endocrine-or HER2-targeted therapies. The prevailing view is that targeting the insulin-like growth factor (IGF) signal transduction pathway will not be beneficial for triple-negative breast cancers because their growth is not IGF-responsive. The present study investigates the importance of IGFs in the proliferation and survival of triple-negative breast cancer cells. Estrogen and progesterone receptors, HER2, type I IGF, and insulin receptors were measured by Western transfer analysis. The effects of IGF-1 on proliferation were assessed by DNA quantitation and on cell survival by poly (ADP-ribose) polymerase cleavage. The effect of IGF-1 on phosphorylation of the IGF receptors, Akt and mitogen-activated protein kinase, was measured by Western transfer analysis. Seven cell lines were identified as models of triple-negative breast cancer and shown to express IGF receptors at levels similar to those present in estrogen-responsive cell lines known to respond to IGFs. IGF-1 increased the proliferation and cell survival of all triple-negative cell lines. Proliferation was attenuated after reduction of type I IGF receptor expression. Cells that express higher levels of receptor were more sensitive to subnanomolar IGF-1 concentrations, but the magnitude of the effects was not correlated simply with the absolute amount or phosphorylation of the IGF receptors, Akt or mitogen-activated protein kinase. These results show that IGFs stimulate cell proliferation and promote cell survival in triple-negative breast cancer cells and warrant investigation of the IGF signal transduction pathway as a therapeutic target for the treatment triple-negative breast cancer.

Publication metadata

Author(s): Davison Z, de Blacquière GE, Westley BR, May FEB

Publication type: Article

Publication status: Published

Journal: Neoplasia

Year: 2011

Volume: 13

Issue: 6

Pages: 504-515

Print publication date: 01/06/2011

Online publication date: 04/03/2014

Acceptance date: 02/03/2011

Date deposited: 29/04/2015

ISSN (print): 1522-8002

ISSN (electronic): 1476-5586

Publisher: Neoplasia Press

URL: http://dx.doi.org/10.1593/neo.101590

DOI: 10.1593/neo.101590

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