Oncogen

James G Bradley

Gregory D Plowman

Mohammed Shoyab

Vicki Lynn McDonald

A novel cell growth regulatory factor, named Amphiregulin, is described. This extremely hydrophilic glycoprotein, having a median molecular weight of 22,500 daltons, demonstrates unusual biological activity. Amphiregulin is a bifunctional cell growth regulatory factor which exhibits potent inhibitory activity on DNA synthesis in neoplastic cells, yet promotes the growth of certain normal cells. The invention is based, in part, on the discovery that MCF-7 cells, when treated with the tumor promoting agent, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), express and secrete two distinct yet functionally equivalent forms of Amphiregulin. These two forms are structurally identical and perfectly homologous except that the truncated form lacks an amino-terminal hexapeptide found in the larger form. The Amphiregulin gene has been cloned and used to construct plasmids which direct the expression of bioactive Amphiregulin in transformed Escherichia coli cells. A wide variety of uses for Amphiregulin are encompassed by the present invention, including the treatment of wounds and cancers.

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Woodinville, WA, United States of America

James G Bradley