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Elevated Expression of pp60^c-src in Low Grade Human Bladder Carcinomas¹

Laboratory of Cancer Biology, Department of Surgery, New England Deaconess Hospital, Boston, Massachusetts 02115 [P. F., K. B., K. S. S., I. C. S.]; Division of Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts 01803 [J. A. L.]; and Department of Urology, Kings College Hospital, London SE59RS, United Kingdom [A. D. J.]

The results presented in this report demonstrate that the tyrosine-specific protein kinase activity of pp60^c-arc is elevated over that recorded in normal bladder mucosa in a subset of human bladder carcinomas. Increased kinase activity was observed mainly in low grade bladder lesions and was associated, at least in part, with elevated levels of pp60^c-arc expression. Extension of this analysis to a panel of human bladder carcinoma cell lines confirmed previous observations of low pp60^c-arc kinase activity in three lines established from high grade (GIII) bladder tumors and revealed increased kinase activity in three alternative bladder lines derived from GI or GII tumors. Use of an anti-phosphotyrosine antibody in Western blot analysis revealed the presence of novel phosphotyrosyl cellular substrates in human bladder cell lines and tumors displaying elevated pp60^c-arc kinase activity. These observations suggest an association for the src protooncogene in urothelial cell differentiation events.

¹ This work was supported by NIH Grants CA42944 and CA44704.

Received 9/16/91. Accepted 1/ 8/92.