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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.05.2009 | Original Paper

Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling

verfasst von: Sebastian Zimmer, Philip Kahl, Theresa M. Buhl, Susanne Steiner, Eva Wardelmann, Sabine Merkelbach-Bruse, Reinhard Buettner, Lukas C. Heukamp

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 5/2009

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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.

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Titel: Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling
verfasst von: Sebastian Zimmer
Philip Kahl
Theresa M. Buhl
Susanne Steiner
Eva Wardelmann
Sabine Merkelbach-Bruse
Reinhard Buettner
Lukas C. Heukamp
Publikationsdatum: 01.05.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 5/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-008-0509-9

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Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling

Abstract

Purpose

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Results

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Springer Medizin

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Results

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