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Journal of Mammary Gland Biology and Neoplasia

Published in:

01-06-2008

The Role of ErbB3 and its Binding Partners in Breast Cancer Progression and Resistance to Hormone and Tyrosine Kinase Directed Therapies

Author: Anne W. Hamburger

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 2/2008

Abstract

An increasingly important role for the ErbB3 receptor in the genesis and progression of breast cancer is emerging. ErbB3 is frequently overexpressed in breast cancer and coexpression of ErbB2/3 is a poor prognostic indicator. ErbB3 has also been implicated in the development of resistance to antiestrogens such as tamoxifen and ErbB tyrosine kinase inhibitors such as gefitinib. Persistent activation of the AKT pathway has been postulated to contribute to ErbB3-mediated resistance to these therapies. This activation may be due in part to the inappropriate production of the ErbB3 ligand heregulin. ErbB3 binding proteins, which negatively regulate ErbB3 protein levels and the ability of ErbB3 to transmit proliferative signals, also contribute to breast cancer progression and treatment resistance. These proteins include the intracellular RING finger E3 ubiquitin ligase Nrdp1 and the leucine-rich protein LRIG-1 that mediate receptor degradation. Ebp1, another ErbB3 binding protein, suppresses HRG driven breast cancer cell growth and contributes to tamoxifen sensitivity. These studies point to the importance of the evaluation of protein levels and functional activity of ErbB3 and its binding proteins in breast cancer prognosis and prediction of clinical response to treatment.

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Title: The Role of ErbB3 and its Binding Partners in Breast Cancer Progression and Resistance to Hormone and Tyrosine Kinase Directed Therapies
Author: Anne W. Hamburger
Publication date: 01-06-2008
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 2/2008
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-008-9077-5

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