Induction of in Vitro Differentiation of Mouse Erythroleukemia Cells by Genistein, an Inhibitor of Tyrosine Protein Kinases1

We have found that genistein, a specific inhibitor of tyrosine protein kinases, induces in vitro erythroid differentiation of mouse erythroleukemia cells. Characterization of the induction process indicated that the genistein-induced differentiation is different from that induced by conven tional inducing agents such as dimethyl sulfoxide or hexamethylenebisacetamide. This conclusion was based upon the earlier appearance of differentiated cells, insensitivity to a specific inhibitor (dexamethasone), and responsiveness of some of the differentiation-resistant cells to genistein in the genistein-induced erythroid differentiation. Possible biological significance of this finding is discussed with respect to the involvement of protein phosphorylation (or dephosphorylation) in mouse erythroleukemia cell differentiation.