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

01-06-2008

ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer

Author: David F. Stern

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

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Abstract

ERBB3/HER3 is one of the four members of the epidermal growth factor receptor (ERBB) family. It is activated by binding to ligands Neuregulin-1 and Neuregulin-2. Since ERBB3 lacks intrinsic kinase activity, signal transduction occurs through formation of heterodimers with EGFR, ERBB2, and ERBB4. ERBB3 is a signaling specialist since it has six binding sites for the p85 SH2 adapter subunit of phosphoinositide 3’ kinases. These lipid kinases coordinate regulation of metabolism, cell size, proliferation, survival, and angiogenesis. Not surprisingly, ERBB3 signaling has been linked to cancer etiology and progression. In breast cancer, the partnership of ERBB2 and ERBB3 may be crucial for the aggressive properties of cancers with ERBB2 amplification, and may contribute to pre-existing and acquired resistance to therapy. This partnership creates opportunities for improving efficacy of ERBB-targeted pharmaceuticals, by interfering with coupling of ERBB2 to ERBB3 through dimerization inhibitors, and by use of therapeutic compounds that target AKT-dependent pathways activated through ERBB3. Additional therapeutic opportunities may be identified through better understanding of how ERBBs are regulated and deployed in normal mammary gland processes. Work using mouse models has identified the main processes regulated by each of the four ERBBs, which has practical implications in understanding breast cancer etiology, and eventual development of better prognostic, predictive, and therapeutic tools.

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Metadata
Title
ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer
Author
David F. Stern
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/s10911-008-9083-7

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