EGF-Related Peptides and Their Receptors in Mammary Gland Development

The discovery of multiple EGF-like ligands and erbB receptors offers the potential for a highly diverse signaling system allowing specific ligand/receptor complexes to be created in response to a certain hormone(s) or stage of mammary development. The known erbB receptors and several of the erbB-related ligands are synthesized by the normal mammary gland and have different temporal and spatial expression patterns. For instance, cumulative findings support the concepts that the EGF receptor has an essential role in morphogenesis of the mammary gland and that activation of this receptor occurs in response to estradiol-stimulated synthesis of an EGF receptor ligand in mammary stromal cells. The importance of both epithelial and stromal mammary cells in the hormonal activation of erbB-related pathways is underscored in this review. Current experimental protocols that utilize erbB mutant mice or enable detection of phosphorylated erbB members and their proximal substrates should permit more precise identification of the pathways operative in the mammary gland.