ABSTRACT The ErbB family of receptor tyrosine kinases has four members, EGFR, ErbB2, ErbB3 and ErbB4. Although the causal roles of EGFR and ErbB2 overexpression in breast cancer have been intensely studied, less attention has been paid to ErbB3 and ErbB4. However, several recent studies demonstrate an increasing research interest in ErbB3 and ErbB4 as potential therapeutic targets in breast cancers. The signaling pathways at play in breast cancers are often the same pathways that drive cell growth and survival in the untransformed breast epithelium. The roles of ErbB3 and ErbB4 in the normal mammary epithelium have been studied in depth using genetically engineered mouse models. This review will discuss ErbB3 and ErbB4 signaling pathways in the context of epithelial diversity in the breast throughout the many developmental phases that characterize the breast, and we will relate their physiological functions to potential parallels in breast tumorigenesis and malignant progression.
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