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O-Phospho-L-tyrosine Inhibits Cellular Growth by Activating Protein Tyrosine Phosphatases¹

Department of Pathology, University of Maryland Cancer Center, Baltimore, Maryland 21201

O-Phospho-L-tyrosine (P-Tyr), a substrate for a wide range of protein tyrosine phosphatases, inhibited growth of human renal and breast carcinoma cells. Growth was blocked in the S phase of the cell cycle. A decrease in the amount of cyclin proteins A and B was also observed. P-Tyr incubation led to activation of cellular protein tyrosine phosphatases resulting in the inhibition of tyrosine phosphorylation of epidermal growth factor receptor as well as of p34^cdc2. P-Tyr synergistically sensitized the renal carcinoma ACHN cells to killing by the chemotherapeutic agents doxorubicin and etoposide. These growth inhibitory properties of P-Tyr in vitro suggest its possible use as an anticancer agent.

¹ This work was funded by NIH Grant R01HL 42069 awarded to A. W. H.

² To whom requests for reprints should be addressed, at Dept. of Pathology, University of Maryland Cancer Center, 655 W. Baltimore St., Bressler Research Bldg., Room 9-051, Baltimore, MD 21201.

Received 7/14/92. Accepted 11/19/92.