Mechanisms for the escape of breast cancer cells from normal growth controls are being evaluated in human and rodent tissues. Two growth inhibitors and two growth stimulatory factors have been isolated from breast tissues, breast fluids, and/or breast cell lines. Two of the factors were shown to be transforming growth factor alpha (TGF ) and transforming growth factor beta (TGF ). The former was made by normal breast cells and by some tumors. Its synthesis appeared to be regulated by estrogenic hormones. The latter factor was synthesized in similar amounts by normal and neoplastic mammary epithelium. Two other growth modulators isolated from human breast tissues and/or milk represent activities not described by other groups. One was mammary-derived growth factor I (MDGFI), a 62-kD peptide that greatly enhanced normal mammary cell proliferation and basement membrane synthesis MDGFI was purified to apparent homogeneity and its N-terminal sequence determined. There was no homology with any known protein. The fourth factor, mammary inhibitory factor (MIA) was also purified to apparent homogeneity and sequenced. MIA was shown to be 95% homologous with the N-terminal sequence of -lactalbumin. Both normal and cancer cell lines from human breast were inhibited by MIA; in general the normal cells were more sensitive to it. Alpha- lactalbumins from several species (cow, human, monkey, mouse, rat, and camel) were all inhibitory at low concentrations (1-10 ng/ml).
