Abstract
The regulation of normal breast development is dependent on several hormones. Among these hormones, estrogens are the most well-characterized and they perform an essential role in the control of normal mammary development and in the etiology and progression of breast cancer. In addition, normal and malignant mammary epithelial and stromal cells synthesize locally acting growth factors that function through autocrine, juxtacrine, and paracrine pathways. Several studies have demonstrated that estrogens influence mammary epithelial-cell growth both directly and indirectly by modulating growth-factor production and growth-factor receptor expression (1). The epidermal growth factor (EGF)-family of peptides, in combination with their cognate receptors, is significantly involved in the regulation of mammary-gland development, morphogenesis and lactation, and also plays a pivotal role in the pathogenesis of human breast cancer (2) (Table 1 and Fig. 1). In fact, the morphological changes during mammary-gland development are accompanied by changes in the pattern of expression of EGF-related peptides in mammary epithelial and stromal cells. EGF, amphiregulin (AR), transforming growth factor a (TGF-α), cripto-1 (CR-1), and heregulin α (HRG-α) are expressed in the virgin mouse mammary gland in ductal epithelial cells (EGF, AR) and in the cap stem cells (TGF-α, CR-1) of the growing terminal end buds. In contrast, HRG-α expression is detected during pregnancy and lactation in a subpopulation of mesenchymal cells (3,4). In addition, experiments using slow-release Elvax pellets containing EGF, TGF-α, HRG-α, or β1 implanted in the virgin mammary gland of ovariectomized mice have shown that these peptides stimulate lobulo-alveolar development (5). Recent experiments have shown that transformation of mammary epithelial cells might result from increased production or response to stimulatory growth factors. In fact, TGF-a can act as a transforming gene when overexpressed in mouse and human mammary epithelial cells in vitro or in vivo (6, 7). In addition, activation of cellular proto-oncogenes such as c-Ha-ras and c-erbB-2 in mouse and human mammary epithelial cells leads to cellular transformation and to the up-regulation of expression of several different EGF-related peptides (8).KeywordsEpidermal Growth Factor ReceptorMammary Epithelial CellHuman Mammary Epithelial CellEpidermal Growth Factor FamilyEpidermal Growth Factor Family MemberThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Published Version
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