The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

OBJECTIVES: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines. MATERIALS AND METHODS: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinas...

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Autores principales: Pickhard, Anja, Siegl, Michael, Baumann, Alexander, Huhn, Maximilian, Wirth, Markus, Reiter, Rudolf, Rudelius, Martina, Piontek, Guido, Brockhoff, Gero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170642/
https://www.ncbi.nlm.nih.gov/pubmed/24980817
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author Pickhard, Anja
Siegl, Michael
Baumann, Alexander
Huhn, Maximilian
Wirth, Markus
Reiter, Rudolf
Rudelius, Martina
Piontek, Guido
Brockhoff, Gero
author_facet Pickhard, Anja
Siegl, Michael
Baumann, Alexander
Huhn, Maximilian
Wirth, Markus
Reiter, Rudolf
Rudelius, Martina
Piontek, Guido
Brockhoff, Gero
author_sort Pickhard, Anja
collection PubMed
description OBJECTIVES: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines. MATERIALS AND METHODS: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting. RESULTS: Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27). CONCLUSION: This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.
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spelling pubmed-41706422014-09-22 The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism Pickhard, Anja Siegl, Michael Baumann, Alexander Huhn, Maximilian Wirth, Markus Reiter, Rudolf Rudelius, Martina Piontek, Guido Brockhoff, Gero Oncotarget Research Paper OBJECTIVES: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines. MATERIALS AND METHODS: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting. RESULTS: Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27). CONCLUSION: This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown. Impact Journals LLC 2014-06-18 /pmc/articles/PMC4170642/ /pubmed/24980817 Text en Copyright: © 2014 Pickhard et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pickhard, Anja
Siegl, Michael
Baumann, Alexander
Huhn, Maximilian
Wirth, Markus
Reiter, Rudolf
Rudelius, Martina
Piontek, Guido
Brockhoff, Gero
The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title_full The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title_fullStr The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title_full_unstemmed The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title_short The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
title_sort response of head and neck squamous cell carcinoma to cetuximab treatment depends on aurora kinase a polymorphism
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170642/
https://www.ncbi.nlm.nih.gov/pubmed/24980817
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