Oncotarget

Research Papers:

HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas

Michalis V. Karamouzis, Georgia Dalagiorgou, Urania Georgopoulou, Afroditi Nonni, Michalis Kontos and Athanasios G. Papavassiliou _

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Oncotarget. 2016; 7:5576-5597. https://doi.org/10.18632/oncotarget.6762

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Abstract

Michalis V. Karamouzis1, Georgia Dalagiorgou1, Urania Georgopoulou2, Afroditi Nonni3, Michalis Kontos4, Athanasios G. Papavassiliou1

1Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece

2Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece

3First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece

4Department of Propaedeutic Surgery, Medical School, National and Kapodistrian University of Athens, ‘Laikon’ General Hospital, 11527 Athens, Greece

Correspondence to:

Athanasios G. Papavassiliou, e-mail: papavas@med.uoa.gr

Keywords: HER-3, ErbB, dimerization pattern, proximity ligation assay, breast cancer

Received: September 13, 2015    Accepted: December 22, 2015    Published: December 26, 2015

ABSTRACT

Breast carcinogenesis is a multi-step process in which membrane receptor tyrosine kinases are crucial participants. Lots of research has been done on epidermal growth factor receptor (EGFR) and HER-2 with important clinical results. However, breast cancer patients present intrinsic or acquired resistance to available HER-2-directed therapies, mainly due to HER-3. Using new techniques, such as proximity ligation assay, herein we evaluate the dimerization pattern of HER-3 and the importance of context-dependent dimer formation between HER-3 and other HER protein family members. Additionally, we show that the efficacy of novel HER-3 targeting agents can be better predicted in certain breast cancer patient sub-groups based on the dimerization pattern of HER protein family members. Moreover, this model was also evaluated and reproduced in human paraffin-embedded breast cancer tissues.


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