Document Detail


Detection and downregulation of type I IGF receptor expression by antibody-conjugated quantum dots in breast cancer cells.
MedLine Citation:
PMID:  18418709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The type I insulin-like growth factor (IGF) receptor (IGF1R) is a transmembrane tyrosine kinase involved in breast cancer proliferation, survival, and metastasis. Several monoclonal antibodies directed against the receptor are in clinical trials. In order to develop a methodology to detect and measure IGF1R levels in breast cancer cells, we covalently conjugated an IGF1R antibody, AVE-1642, with quantum dots (Qdots), which are nanocrystals that emit fluorescence upon excitation. AVE-1642 Qdots only bound to cells that express IGF1R, and measured IGF1R levels by fluorescence emission at 655 nm. After binding to the cell surface, AVE-1642 Qdots underwent receptor mediated endocytosis, localized to endosome, and later translocated into the nucleus. Treating MCF-7 cells with AVE-1642 Qdots, but not unconjugated Qdots alone, downregulated IGF1R levels and rendered cells refractory to IGF-I stimulation. Furthermore, cell proliferation was slightly inhibited by AVE-1642 Qdots, but not the unconjugated Qdots. Our data suggest that AVE-1642 Qdots can be used to detect IGF1R expression and measure changes in cell surface receptor levels. In addition, the inhibitory effect of AVE-1642 Qdots to cell proliferation implies that it may serve as a traceable therapeutic agent.
Authors:
Hua Zhang; Deepali Sachdev; Chun Wang; Allison Hubel; Martine Gaillard-Kelly; Douglas Yee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-04-17
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  114     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-04     Completed Date:  2009-04-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  277-85     Citation Subset:  IM    
Affiliation:
University of Minnesota Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology*
Blotting, Western
Breast Neoplasms / metabolism*,  pathology
Cell Line
Cell Membrane / metabolism*
Cell Proliferation
Down-Regulation
Female
Fibroblasts / metabolism,  pathology
Flow Cytometry
Homozygote
Humans
Insulin-Like Growth Factor I / pharmacology
Mice
Mice, Knockout
Quantum Dots*
Receptor, IGF Type 1 / metabolism*
Grant Support
ID/Acronym/Agency:
P30 CA077598/CA/NCI NIH HHS; R01 CA74285/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, IGF Type 1

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