THE BLOOD-GROUP ABO GENE TRANSCRIPT IS DOWN-REGULATED IN HUMAN BLADDER-TUMORS AND GROWTH-STIMULATED UROTHELIAL CELL-LINES

The molecular mechanism that in human bladder tumors leads to the loss of blood group ABO glycosyltransferase activity and, thereby, the los s of ABO antigens was investigated. In 15 tumors and 3 normal biopsies from blood group AB individuals and 7 tumors and 3 normal biopsies fr om blood group O individuals, mRNA was detected by a reverse transcrip tion PCR (RT-PCR) assay, and the ABO blood group structure was determi ned by immunohistology. The RT-PCR spanned several introns in the ABO gene to exclude DNA contamination, and the RT-PCR product was shown to reflect the ABO gene message by dideoxy sequencing. The ABO mRNA was present in normal urothelium and low-grade tumors but disappeared from high grade tumors. This correlation to tumor grade was significant (P < 0.04). Immunohistochemistry with monoclonal anti-blood group antibo dies showed a complete correlation between the presence of mRNA and th e presence of AB carbohydrate structures on cell surfaces. In two urot helial cell lines, genotyped as A/- and A/A, growth stimulation with t he cholera toxin B subunit led to a total loss of ABO mRNA, and epider mal growth factor stimulation had an identical effect on one of the ce ll lines. We conclude that the ABO glycosylation in normal and maligna nt urothelium is regulated at the mRNA level, and that a mechanism ass ociated with cell proliferation may trigger down-regulation of ABO mRN A.