The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches
A. Zaczek1,2, B. Brandt3 and K.P. Bielawski1
1Molecular Diagnostics Division, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Poland, 2Postgraduate School of Molecular Medicine, Warsaw, Poland and 3Institute for Clinical Chemistry and Laboratory Medicine, Westfalische-Wilhelms University of Muenster, Germany
Offprint requests to: Dr. Krzysztof Piotr Bielawski, Molecular Diagnostics Division, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-22 Gdansk, Poland. e-mail: bielawsk@biotech.univ.gda.pl
Summary. The HER family of receptor tyrosine kinase couples binding of extracellular growth factor ligands to intracellular signal transduction pathways, contributing in this fashion to the ability of the cell to respond correctly to its environment. The HER family and its ligands are critically involved in the carcinogenesis of the mammary gland. Abnormal function of the members of HER family resulting in receptor hyper-activation (due to gene amplification, protein overexpression or abnormal transcriptional regulation) has been linked with breast cancer prognosis. It is also extensively studied as the predictive factor and target for therapy. There are clinical indications supporting the concept that none of the receptors: EGFR, HER2, HER3 and HER4 can be considered as the stand-alone receptor in breast cancer development and clinical course of the disease. There is a growing body of evidence that cooperation between them contributes to more aggressive tumor phenotype and influences the response to therapy. This underlines the importance of quantification of all HER family members and indicates the urgent need for implementation of methods that can efficiently and reliably examine four HER receptors as a whole panel in breast cancer patients. Histol Histopathol 20, 1005-1015 (2005)
Key words: HER family of tyrosine kinase receptors, Signaling network, Therapeutic approaches
DOI: 10.14670/HH-20.1005