Transforming growth factor-β and breast cancer: Mammary gland development

Transforming growth factor (TGF)-β(1) is a pluripotent cytokine that profoundly inhibits epithelial proliferation, induces apoptosis, and influences morphogenesis by mediating extracellular matrix deposition and remodeling. The physiologic roles of the action of TGF-β in mammary gland, indeed in most tissues, are poorly understood. In order to understand the actions of TGF-β, we need to take into account the complexity of its effects on different cell types and the influence of context on cellular responses. This task is further compounded by multiple mechanisms for regulating TGF-β transcription, translation, and activity. One of the most significant factors that obscures the action of TGF-β is that it is secreted as a stable latent complex, which consists of the 24-kDa cytokine and the 80-kDa dimer of its prepro region, called latency-associated peptide. Latency imposes a critical restraint on TGF-β activity that is often overlooked.The extracellular process known as activation, in which TGF-β is released from the latent complex, is emphasized in the present discussion of the role of TGF-β in mammary gland development. Definition of the spatial and temporal patterns of latent TGF-β activation in situ is essential for understanding the specific roles that TGF-β plays during mammary gland development, proliferation, and morphogenesis.