Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma.

Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Research Abstract Details 

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Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Abstract Text:

Barbara A Frederick,Barbara A Helfrich,Christopher D Coldren,Di Zheng,Dan Chan,Paul A Bunn,David Raben,

The modest response of patients with head and neck squamous cell carcinoma (HNSCC) and non-small cell lung carcinoma (NSCLC) to epithelial growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib indicates the need for the development of biomarkers to predict response. We determined gefitinib sensitivity in a panel of HNSCC cell lines by a 5-day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and confirmed these responses with analysis of downstream signaling by immunoblotting and cell cycle arrest. Basal gene expression profiles were then determined by microarray analysis and correlated with gefitinib response. These data were combined with previously reported NSCLC microarray results to generate a broader predictive index. Common markers of resistance between the two tumor types included genes associated with the epithelial to mesenchymal transition. We confirmed that increased protein expression of vimentin combined with the loss of E-cadherin, claudin 4, and claudin 7 by immunoblotting was associated with gefitinib resistance in both HNSCC and NSCLC cell lines. In addition, the loss of the Ca(2+)-independent cell-cell adhesion molecules EpCAM and TROP2 in resistant lines was confirmed by immunofluorescence. Tumor xenografts derived from the gefitinib-sensitive UM-SCC-2 were growth-delayed by gefitinib, whereas the gefitinib-resistant 1483 xenografts were unaffected. These data support a role for epithelial to mesenchymal transition in establishing gefitinib resistance for both HNSCC and NSCLC, and indicate that clinical trials should address whether these biomarkers will be useful for patient selection.

Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Publishing Authors By Initials

BA Frederick,BA Helfrich,CD Coldren,D Zheng,D Chan,PA Bunn,D Raben,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: quinazolines research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: quinazolines research

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Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular cancer therapeutics

VOLUME: 6

Page Numbers: 1683-91

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 31

MONTH: 05

YEAR: 2007

Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Information

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LANGUAGE: eng

NlmUniqueID: 101132535

Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Keywords Mesh Terms:

KEYWORDS: Quinazolines

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Information

Substance Name: gefitinib

Registry Number: 184475-35-2

Grant and Affiliation Information for Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma.

AFFILIATION: Departments of Radiation, University of Colorado at Denver Health Sciences Center, Aurora, Colorado 80010, USA. Barbara.frederick@UCHSC.edu

Country: United States

AGENCY: United States NCI

GRANT: P50 CA058187

ACRONYM: CA

MEDLINETA: Mol Cancer Ther

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