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Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Kashyap, Abhishek, Hollier, Brett G., Manton, Kerry, Satyamoorthy, K., Leavesley, David I., & Upton, Zee (2011) Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration. Endocrinology, 152(4).

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Abstract

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways.

Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue ([L24][A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

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14 citations in Web of Science®

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45 since deposited on 03 Mar 2011
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ID Code: 40398
Item Type: Journal Article
Additional URLs:
Keywords: Migration, IGF Binding Protein, Insulin-Like Growth Factor, Vitronectin, Breast Cancer
DOI: 10.1210/en.2010-0897
ISSN: 0013-7227
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cellular Interactions (incl. Adhesion Matrix Cell Wall) (060106)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Signal Transduction (060111)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 Endocrine Society
Deposited On: 03 Mar 2011 11:44
Last Modified: 01 Mar 2012 00:10

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