title: HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas.
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.
authors.affiliation: Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Michalis V
authors.initials: MV
authors.lastname: Karamouzis
authors.affiliation: Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Dalagiorgou
authors.affiliation: Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece.
authors.forename: Urania
authors.initials: U
authors.lastname: Georgopoulou
authors.affiliation: First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Afroditi
authors.initials: A
authors.lastname: Nonni
authors.affiliation: Department of Propaedeutic Surgery, Medical School, National and Kapodistrian University of Athens, 'Laikon' General Hospital, 11527 Athens, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Kontos
authors.affiliation: Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D055503:Protein Multimerization / Q000187:drug effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3
keywords: ErbB; HER-3; breast cancer; dimerization pattern; proximity ligation assay