Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling |
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Authors: | Sebastian Zimmer Philip Kahl Theresa M Buhl Susanne Steiner Eva Wardelmann Sabine Merkelbach-Bruse Reinhard Buettner Lukas C Heukamp |
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Institution: | (1) Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany |
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Abstract: | Purpose The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) has
been linked to activating mutations in the EGFR gene. So far these mutations have been extensively characterized in established
cell lines. The aim of this study was to determine the effects of EGFR mutations on downstream signaling in human tumor specimens.
Methods We have looked for mutations of the EGFR gene in specimens of 67 patients with NSCLC and correlated these with EGFR phosphorylation
and the activity of its three main downstream signaling cascades Akt, MAPK and Stat3 by immunohistochemistry.
Results We show that the phosphorylation of tyrosine residues 922 and 1173, but not 1068, are primarily affected by the activating
EGFR mutations. Akt activity was significantly higher in patients with EGFR mutations but we found no difference in Stat3
or MAPK phosphorylation. Our results suggest that EGFR mutations not only increase receptor activity, but also alter responses
of downstream signaling cascades in human NSCLCs and that these finding differ from results obtained in cell lines.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | EGFR NSCLC Akt MAPK Stat3 |
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