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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2009-5-13
pubmed:abstractText
Nanoparticle quantum dots (QDs) provide sharper and more photostable fluorescent signals than organic dyes, allowing quantification of multiple biomarkers simultaneously. In this study, we quantified the expression of epidermal growth factor receptor (EGFR) and E-cadherin (E-cad) in the same cells simultaneously by using secondary antibody-conjugated QDs with two different emission wavelengths (QD605 and QD565) and compared the cellular distribution of EGFR and E-cad between EGFR-tyrosine kinase inhibitor (TKI)-insensitive and -sensitive lung and head and neck cancer cell lines. Relocalization of EGFR and E-cad upon treatment with the EGFR-TKI erlotinib in the presence of EGF was visualized and analyzed quantitatively. Our results showed that QD-immunocytochemistry (ICC)-based technology can not only quantify basal levels of multiple biomarkers but also track the localization of the biomarkers upon biostimulation. With this new technology we found that in EGFR-TKI-insensitive cells, EGFR and E-cad were located mainly in the cytoplasm; while in sensitive cells, they were found mainly on the cell membrane. After induction with EGF, both EGFR and E-cad internalized to the cytoplasm, but the internalization capability in sensitive cells was greater than that in insensitive cells. Quantification also showed that inhibition of EGF-induced EGFR and E-cad internalization by erlotinib in the sensitive cells was stronger than that in the insensitive cells. These studies demonstrate substantial differences between EGFR-TKI-insensitive and -sensitive cancer cells in EGFR and E-cad expression and localization both at the basal level and in response to EGF and erlotinib. QD-based analysis facilitates the understanding of the features of EGFR-TKI-insensitive versus -sensitive cancer cells and may be used in the prediction of patient response to EGFR-targeted therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1361-6528
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
225102
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19433879-Antineoplastic Agents, pubmed-meshheading:19433879-Cadherins, pubmed-meshheading:19433879-Carcinoma, Squamous Cell, pubmed-meshheading:19433879-Cell Line, Tumor, pubmed-meshheading:19433879-Drug Resistance, Neoplasm, pubmed-meshheading:19433879-Endosomes, pubmed-meshheading:19433879-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19433879-Head and Neck Neoplasms, pubmed-meshheading:19433879-Humans, pubmed-meshheading:19433879-Immunohistochemistry, pubmed-meshheading:19433879-Lung Neoplasms, pubmed-meshheading:19433879-Lysosomes, pubmed-meshheading:19433879-Neoplasms, pubmed-meshheading:19433879-Protein Kinase Inhibitors, pubmed-meshheading:19433879-Protein-Tyrosine Kinases, pubmed-meshheading:19433879-Quantum Dots, pubmed-meshheading:19433879-Quinazolines, pubmed-meshheading:19433879-Receptor, Epidermal Growth Factor, pubmed-meshheading:19433879-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Quantum dot-based quantification revealed differences in subcellular localization of EGFR and E-cadherin between EGFR-TKI sensitive and insensitive cancer cells.
pubmed:affiliation
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.