Document Detail


Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines.
MedLine Citation:
PMID:  19337828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The insulin-like growth factor I receptor (IGF1R) interacts with estrogen receptor-alpha (ERalpha) and HER2. We examined the effect of combinations of IGF1R antagonists (alpha-IR3, AG1024) and anti-estrogens (4-hydroxy tamoxifen, fulvestrant) in two human ER+ breast cancer cell lines: BT474 (HER2 overexpressing, IGF1R low) and MCF7 (HER2 non-overexpressing, IGF1R high). In BT474 cells, growth was inhibited by anti-estrogens, but not by IGF1R antagonists; however, adding IGF1R inhibitors to anti-estrogens enhanced growth inhibition. In MCF7 cells, growth was inhibited by IGF1R and ER antagonists and more so by their combination. In both cell lines, no single agents could induce apoptosis, but combining IGF1R inhibitors with anti-estrogens induced dramatic levels of apoptosis. IGF1R antagonists enhanced the ability of the anti-estrogens to inhibit ER transcriptional activity in BT474 cells, but not in MCF7 cells. The drug combination synergistically inhibited ER and IGF1R activity. Such combinations may be useful therapy for breast cancer.
Authors:
Ashok K Chakraborty; Allison Welsh; Michael P Digiovanna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-04-01
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  120     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-16     Completed Date:  2010-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  327-35     Citation Subset:  IM    
Affiliation:
Departments of Internal Medicine (Section of Medical Oncology) and Pharmacology, and the Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, Room WWW217, New Haven, CT 06510, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Hormonal / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects*
Breast Neoplasms / metabolism*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Estrogen Receptor Modulators / pharmacology
Female
Humans
Immunoblotting
Immunoprecipitation
Receptor, IGF Type 1 / antagonists & inhibitors*
Receptors, Estrogen / drug effects,  metabolism
Signal Transduction / drug effects
Transcription, Genetic / drug effects
Tyrphostins / pharmacology
Grant Support
ID/Acronym/Agency:
CA-16359/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/Estrogen Receptor Modulators; 0/Receptors, Estrogen; 0/Tyrphostins; 0/tyrphostin AG 1024; EC 2.7.10.1/Receptor, IGF Type 1

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