A neoplastic human salivary intercalated duct cell line (HSG) and its derivatives, HSG with a myoepithelial cell phenotype (HSG-AZA1) and HSG with an acinar cell phenotype (HSG-AZA3), which were induced by 5-azacytidine treatment of HSG cells, were cultivated in the presence of epidermal growth factor (EGF). Morphological changes occurred; cells that were spindle shaped or stellate and had long cytoplasmic processes appeared in all of the treated cells. Major alterations, such as expression of

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... euron-specific enolase, neurofilaments, or synaptophysin as well as formation of neurite-like structures densely packed with microfibrils and microtubules, were observed in these cells with a phenotype similar to that of neuron-like cells. Both the anchorage-independent and anchorage-dependent growths of the treated HSG cells and only anchorage-dependent growth of the treated HSG-AZA1 cells were suppressed, whereas the anchorage-dependent growth of the treated HSG-AZA3 cells was enhanced according to the increasing concentrations of EGF. In addition, it has been found by statistical analysis that the growth of HSG cells in culture is suppressed and that of HSG-AZA3 cells in culture is stimulated according to the increasing concentrations of EGF added, whereas the growth of cultured HSG-AZA1 cells is hardly affected by EGF treatment. The HSG, HSG-AZA1, and HSG-AZA3 cell had 1.8 x 10(5), 1.83 x 10(5), and 1.34 x 10(5) EGF receptors, respectively. The amounts of the EGF internalized into cells were larger in HSG-AZA3 cells than in HSG or HSG-AZA1 cells. These findings indicate that the conversion of HSG, HSG-AZA1, and HSG-AZA3 cells into neuron-like cells occurs in growth medium containing EGF, with a concomitant modulation of the growth potentials of the cells which were examined in a different manner.