EXPERIMENTAL MAMMARY EPITHELIAL MORPHOGENESIS IN AN IN-VIVO MODEL - EVIDENCE FOR DISTINCT CELLULAR PROGENITORS OF THE DUCTAL AND LOBULAR PHENOTYPE

An in vivo transplantation system has been used to evaluate the develo pmental capacities of specific mouse mammary epithelial cell populatio ns. Specifically, mouse mammary epithelial cells with distinctly limit ed developmental potentials have been identified using this procedure. Two distinct epithelial cell progenitors have been identified by expe riments designed to determine whether basal lobular and ductal phenoty pes could develop independently under conditions imposed by a limiting dilution. The prediction that these separate epithelial progenitors m ust exist was based upon the results from transplantation experiments carried out in epithelium-divested mammary fat pads of syngeneic mice with mammary epithelium from two different transgenic mouse models. Th e results presented here demonstrate the following points: 1) lobular, i.e. secretory, progenitor cells are present as distinct entities amo ng the mammary epithelial cells found in immature virgin female mice; 2) similarly, ductal epithelial progenitors are present within the sam e population; 3) lobular progenitors are present in greater numbers, a lthough both cell populations are extremely small; 4) as expected, som e inocula produce outgrowths with simultaneous development of both lob ular and ductal phenotypes - it is not known whether this indicates co operative interaction between the two epithelial progenitors or signal s the presence of a third progenitor type capable of producing both du ctular and lobular committed daughters; 5) these findings have importa nt consequences in the design of experiments aimed at testing the effe cts of known and putative mammary oncogenes and tumor suppressor genes , using techniques which include cellular transformation in vitro foll owed by in vivo cultivation and evaluation.