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Abstract
Transforming growth factor (TGF)-β1 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.
Highlights
This review describes briefly mammary gland development and discusses the postulated role of transforming growth factor (TGF)-β1 in mammary gland development as evidenced by its effects in mammary epithelial cell culture and animal studies
Despite the apparently normal morphology, we found that the frequency of proliferating cells of the mammary epithelium is significantly elevated in mammary gland, as occurs in other tissues like liver from TGF-β-null mutant heterozygotes [12]
Further characterization of these cells and determination of their ultimate fate in terms of proliferation and differentiation may be informative regarding the cellular mechanisms by which pattern and function are established during mammary gland development. It is clear from a variety of studies in cell culture that TGF-β can have myriad effects, many of which complement each other, but others that appear paradoxic
Summary
This review describes briefly mammary gland development and discusses the postulated role of TGF-β1 in mammary gland development as evidenced by its effects in mammary epithelial cell culture and animal studies. Mammary ductal outgrowth during puberty was accelerated, and mammary epithelial proliferation was increased in young TGF-β1 haploid genotype animals This effect appeared to be stage-specific in that mammary gland whole mounts from adult nulliparous mice were grossly normal in morphology and functionally intact. We found that mammary epithelial TGF-β immunoreactivity was heterogeneous and most intense during periods of proliferation and morphogenesis, suggesting the presence of a distinct subpopulation Further characterization of these cells and determination of their ultimate fate in terms of proliferation and differentiation may be informative regarding the cellular mechanisms by which pattern and function are established during mammary gland development
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