Schematic representation of epithelial–stromal interactions during mammary gland development. The mammary bud originates at the embryonic level and starts proliferating after birth. Pubertal hormones drive the invasion of the fat pad by the generation of epithelial ducts and terminal end buds (TEB). Proliferation and side branching continues until epithelial ducts fill the adult mammary gland. Pregnancy hormones induce the full development and proliferation of the mammary gland and the transformation of the lobular alveoli into milk-secreting ducts. After lactation the mammary gland involutes to return to a nulliparous-like state via apoptosis, redifferentiation and remodeling processes. C/EBP, CCAAT-enhancer-binding protein; CSF, colony-stimulating factor; DDR, discoidin domain receptor; ECM, extracellular matrix; HSPG, heparan sulfate proteoglycan; GH, growth hormone; IGF, insulin-like growth factor; IRF, interferon regulatory factor; MMP, matrix metalloproteinase; NFκB, nuclear factor-κB; Ptc-1, patched-1; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinases.