Milk growth factor (MGF)-induced differentiation of NT2/D1 cells.

The differentiation activity of milk growth factor (MGF, 200 ng/ml), which also has proliferative activity, was investigated in NT2/D1 cells relative to that of retinoic acid (RA, 10(-7) M). MGF suppressed the proliferation of NT2/D1 cells to the same extent as RA after cultivation for 2x4 days. MGF enhanced Fas expression in NT2/D1 cells and prevented the decrease of Fas expression when RA was also added. MGF induced the synthesis of alpha-smooth muscle actin (alpha-SM-actin) in NT2/D1 cells without fibrils, but RA did not have such a potent activity. MGF extended glial fibrillary acidic protein (GFAP) that existed in a local area of NT2/D1 cell cytoplasm. On the other hand, RA enhanced GFAP expression and dispersed it throughout the cells. MGF slightly induced neurofilament-medium size (NF-M) synthesis in NT2/D1 cells that RA induced in the cells. MGF was less effective than RA in stimulating the synthesis of epinephrine in the cells, and the additive effect of MGF and RA enhanced epinephrine synthesis. While dopamine synthesis was less effectively stimulated by MGF than by RA, an additive effect of MGF and RA for dopamine synthesis was not observed in the cells. It was thus found that MGF differentiated NT2/D1 cells through alpha-SM-actin-synthesis.