Production of Mammastatin, a Tissue-Specific Growth Inhibitor, by Normal Human Mammary Cells

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Abstract
The growth of human mammary cells may be regulated by a balance between growth stimulatory and growth inhibitory pathways. Polypeptides of 47 and 65 kilodaltons (mammastatin) were isolated from conditioned medium of normal human mammary cells. Monoclonal antibodies against mammastatin were generated that blocked its activity and were used for purification and further characterization of the protein. Mammastatin inhibited the growth of 5 transformed human mammary cell lines, but had no effect on the growth of 11 transformed human cell lines derived from nonmammary tissues. Mammastatin appeared to be a heat-labile protein distinct from transforming growth factor-β (TGF-β). By immunoperoxidase staining it was detected in cultured normal human mammary cells, but was decreased in transformed mammary cells.