LacZ = β-galactosidase (Escherichia coli); TGF-β1 = transforming growth factor-beta 1; WAP = whey acidic protein.Available online http://breast-cancer-research.com/content/4/2/047
IntroductionEvidence for mammary epithelial stem cells derives from studies of the glands from rodents, canines and humans. In the human, genetic analysis [1] of contiguous portions of individual human mammary ducts within the same breast signifies their clonal derivation and forecasts the existence of multipotent mammary epithelial cells in the human breast [2][3][4]. This work was confirmed and extended by the demonstration of a common loss of heterozygosity in normal cells in individual lobules within breast tissue from patients with carcinoma, in duct-lobular units from paraffin-embedded mammary tissue, and from normal luminal and myoepithelial cell clones derived from reduction mammoplasty patients [5][6][7].Cell lines from canine mammary spindle-cell tumors exhibited mixed phenotypes on transplantation but possessed identical allelic patterns in microsatellite analysis, suggesting that canine mammary tumors arise from pluripotent stem cells [8].Rat mammary glands contain a subpopulation of clonogenic epithelial cells that, when transplanted, give rise either to alveolar or ductal structures [9]. In quantitative rat mammary cell transplantation studies, both alveolar and ductal colonies were developed that support the conclusion that both colony types are derived from a single clonogenic mammary cell [10,11].In the mouse, it was recently shown that the epithelial population of a fully developed lactating mammary outgrowth in mice could consist of the progeny from a single cell [12]. Serial transplantation of epithelial fragments from the clonally derived gland demonstrated that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. All epithelial cell types were found to be present within these clonal normal populations including luminal, myoepithelial, ductal and lobule-committed epithelial progenitors and fully competent mammary epithelial stem cells. These observations demonstrate the presence of multipotent
AbstractThe existing paradigms for stem cells in adult tissues include the integument, the alimentary canal, the lung, the liver, skeletal muscle and bone marrow. The mammary gland, by contrast, is the 'new kid on the block'. What little is known about stem cells in the mammary gland indicates that they possess a prodigious capacity for self-renewal. More importantly, in rodents, they persist with undiminished reproductive vigor throughout the organism's lifetime without regard to age or reproductive history. Do these stem cells represent primary targets for mammary neoplasia? If so, what are the implications for prevention/therapy?