| IGFBP-3 can either inhibit or enhance EGF-mediated growth of breast epithelial cells dependent upon the presence of fibronectin. | |
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MedLine Citation:
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PMID: 20851879 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Progression of breast cancer is associated with remodeling of the extracellular matrix, often involving a switch from estrogen dependence to a dependence on EGF receptor (EGFR)/HER-2 and is accompanied by increased expression of the main binding protein for insulin-like growth factors (IGFBP-3). We have examined the effects of IGFBP-3 on EGF responses of breast epithelial cells in the context of changes in the extracellular matrix. On plastic and laminin with MCF-10A normal breast epithelial cells, EGF and IGFBP-3 each increased cell growth and together produced a synergistic response, whereas with T47D breast cancer cells IGFBP-3 alone had no effect, but the ability of EGF to increase cell proliferation was markedly inhibited in the presence of IGFBP-3. In contrast on fibronectin with MCF-10A cells, IGFBP-3 alone inhibited cell growth and blocked EGF-induced proliferation. With the cancer cells, IGFBP-3 alone had no effect but enhanced the EGF-induced increase in cell growth. The insulin-like growth factor-independent effects of IGFBP-3 alone on cell proliferation were completely abrogated in the presence of an EGFR, tyrosine kinase inhibitor, Iressa. Although IGFBP-3 did not affect EGFR phosphorylation [Tyr(1068)], it was found to modulate receptor internalization and was associated with activation of Rho and subsequent changes in MAPK phosphorylation. The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor. |
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Authors:
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Jamie McIntosh; Godwin Dennison; Jeff M P Holly; Caroline Jarrett; Alexandra Frankow; Emily J Foulstone; Zoe E Winters; Claire M Perks |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-17 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-01-10 Revised Date: 2011-12-13 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38788-800 Citation Subset: IM |
Affiliation:
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School of Clinical Sciences, IGFs and Metabolic Endocrinology Group, Learning and Research Building, 2nd Floor, University of Bristol, Southmead Hospital, Bristol BS10 5NB, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biotinylation Breast / metabolism* Breast Neoplasms / metabolism* Cell Line, Tumor Epidermal Growth Factor / metabolism* Fibronectins / chemistry* Gene Expression Regulation, Neoplastic* Humans Insulin-Like Growth Factor Binding Protein 3 / metabolism* Laminin / chemistry MAP Kinase Signaling System Phosphorylation Quinazolines / pharmacology Radioimmunoassay rho-Associated Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Fibronectins; 0/Insulin-Like Growth Factor Binding Protein 3; 0/Laminin; 0/Quinazolines; 184475-35-2/gefitinib; 62229-50-9/Epidermal Growth Factor; EC 2.7.11.1/rho-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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