The project consists of analyses of growth and differentiation in a preneoplastic lesion of the mouse mammary gland, the hyperplastic alveolar nodules (HAN). Cell culture methodology will be used to compare selected properties of these HANs with the same properties of cells from normal (midpregnant) and neoplastic epithelium of the mouse mammary gland. Emphasis will be on regulation of mammary function, including the progression to neoplasia, by exogenous factors, hormones and mesenchymal stroma. Accordingly, the three types of cell will be grown in media containing, in various permutations, serum, mesenchymal extract, and several hormones known to govern mammary function. Growth responses will be carefully compared under these several conditions, by measuring DNA accumulation. The regulation of lactose production by the same culture medium factors will be determined. These studies should pinpoint key changes in exogenous regulation of growth and development during neoplastic progression. The idea is to learn just how differentiated function ceases as neoplastic growth commences, since the two seem to be mutually exclusive in mouse mammary tumor cells.