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

Institute of Applied Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

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 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.

¹ This research was supported by a grant from the Japanese Ministry of Education and the CIBA-GEIGY Foundation (Japan).

² To whom requests for reprints should be addressed.

Received 5/24/90. Accepted 11/12/90.

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