Induction of in vitro differentiation of mouse erythroleukemia cells by genistein, an inhibitor of tyrosine protein kinases.

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 conventional inducing agents such as dimethyl sulfoxide or hexamethylene-bisacetamide. 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.