Effects of androgen and antiandrogen on growth, morphology and synthesis of specific proteins in mouse mammary carcinoma cells

Primary cell cultures derived from an androgen-dependent mouse mammary carcinoma, the Shionogi SC-115 tumor, display characteristic changes in growth, morphology and protein synthesis according to the presence or absence of testosterone. In the presence of testosterone, cell proliferation was increased and cells formed characteristic clones having no contact inhibition. Ultrastructural studies of cells showed close contacts of plasma membranes having little or no gap between cells. Some cells were related by bridges of extracellular matrix. Testosterone-induced synthesis of several intracellular and secreted proteins was observed after 35S]methionine-labeling of cells, SDS-PAGE and autoradiography, as well as the disappearance of a protein in androgen-treated cells. In the absence of testosterone, cells grow as a monolayer, have contact inhibition and flattened morphology. The ultrastructurally observed cell-to-cell contacts were usually less intimate, showing spaces of irregular width between cells. None of the testosterone-induced proteins were observed in the absence of hormone. The antiandrogen cyproterone acetate, which by itself was inactive, completely suppressed the androgen-induced effects on growth, morphology and specific protein synthesis. Glycosylation of membrane proteins, as measured after labeling of cells with 3H]N-acetyl-D-glucosamine, was increased by approximately 30% in the presence of testosterone. A similar observation was made in situ by autoradiography on intact cells. Finally, we found that culture medium conditioned by testosterone-treated Shionogi cells had significant mitogenic activity on L-929 mouse fibroblasts.