ELEVATED EXPRESSION OF THE CDC25A PROTEIN PHOSPHATASE IN COLON-CANCER

The nuclear protein phosphatase cdc25A has been postulated to be a pro tooncogene. The total nuclear phosphotyrosyl protein phosphatase (PTP) activity and the expression of cdc25A were compared in normal and can cerous colon epithelial tissue. Nuclei derived from normal mucosal epi thelium and tumors were analyzed for phosphotyrosyl protein phosphatas e activity using the malachite green assay and a synthetic phosphotyro syl peptide based on the sequence of cdc2, a known cdc25A phosphotyros yl protein substrate. Tumorigenesis resulted in elevated nuclear PTP a ctivity (343.0 +/- 37.0% of normal epithelial PTP activity) in 52% (29 of 56) of colon tumors. In all cases elevated nuclear PTP activity co rrelated with an increase in the expression of cdc25A. The changes in PTP activity observed were not due to any increase in the rate of grow th of the colonic mucosa as no corresponding changes occurred with PTP activity under conditions of rapid mucosal growth. (C) 1998 Academic Press.