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

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 resis...

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Bibliographic Details
Published in:Oncotarget 2016-02, Vol.7 (5), p.5576-5597
Main Authors: Karamouzis, Michalis V, Dalagiorgou, Georgia, Georgopoulou, Urania, Nonni, Afroditi, Kontos, Michalis, Papavassiliou, Athanasios G
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Transformation, Neoplastic - drug effects
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Protein Multimerization - drug effects
Receptor, ErbB-2 - metabolism
Receptor, ErbB-3 - antagonists & inhibitors
Receptor, ErbB-3 - metabolism
Research Paper
Signal Transduction
Tumor Cells, Cultured
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.6762