Identification of human milk α-lactalbumin as a cell growth inhibitor

Autor: Thompson, M. P., Farrell, H. M., Mohanam, Sanjeeva, Liu, Sue, Kidwell, W. R., Bansal, M. P., Cook, R. G., Medina, D., Kotts, Claire E., Bano, Mozeena
Zdroj: Protoplasma; December 1992, Vol. 167 Issue: 3-4 p134-144, 11p
Abstrakt: Summary A growth inhibitory protein, mammary inhibitory activity (MIA), was purified to apparent homogeneity from human milk. At concentrations of 5 to 10 ng/ml, the factor inhibited the growth of mammary epithelial cells by 30–80% and also inhibited the growth of normal rat kidney cells. Whereas the cell division of normal human mammary epithelium in primary culture was inhibited by MIA, cell division by fibroblasts from the same tissues was unresponsive. Inhibition was dose and time dependent and readily reversed when MIA was removed. MIA also inhibited growth in culture for three cell lines. The growth inhibitory protein migrated as a 14 kDa protein under reducing conditions on polyacrylamide gels in the presence of sodium dodecyl sulfate. The apparent isoelectric point was pI 5.0. The amino acid composition of MIA resembled that of a-lactalbumin, and sequence analysis of the N-terminal region comprising residues 1–24 and an isolated peptide were identical with the N-terminal and residues 66–81 of human a-lactalbumin. In addition, MIA was active in the lactose synthase system. The results strongly suggest that MIA and a-lactalbumin are identical proteins. Consistent with these results, a-lactalbumin preparations from several mammalian species, including human, goat, cow and camel, were all found to be growth inhibitory for cultured mammary epithelial cells. The inhibitory activity associated with human a-lactalbumin was destroyed by digestion with pepsin or chymotrypsin, by carboxymethylation of cysteine, or by cleavage of methionine 90 following cyanogen bromide treatment. The results raise the possibility that during lactation a-lactalbumin, a product of mammary cell differentiation, could be a physiologically relevant feed-back inhibitor of mammary cell growth and perhaps of other cell types as well.
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