MAUB IS A NEW MUCIN ANTIGEN ASSOCIATED WITH BLADDER-CANCER

The M344 tumor-associated antigen, expressed in 70% of superficial bla dder tumors, is a sialylated carbohydrate present on a high molecular mass thiol-reducible secreted mucin, which we named MAUB for mucin ant igen of the urinary bladder, Herein we studied the relationship betwee n MAUB and other known mucins in the MGH-U3 bladder cancer line where MAUB expression is modulated by culture conditions, Northern blots, im munoradiometric assays, and Western blots showed that only MUC1 and MU C2 are expressed in this MAUB-positive cell line, MUC1 differs from MA UB by its molecular mass and its non-oligomeric nature, while MUC2 has similar molecular mass and response to culture conditions. However, i n double determinant immunoradiometric assays, MAUB and MUC2 did not c ross react. Moreover, confocal microscopy showed different subcellular localization of the two antigens, Treatment of MGH-U3 cells with MUC2 antisense oligodeoxynucleotides resulted in decreased expression of M UGS and increased expression of MAUB, ruling out the possibility that monoclonal antibody M344 recognizes a different glycosylated form of M UC2, In addition, we identified a tumor specimen expressing MAUB but n o MUC2 antigen or mRNA. Together, these results suggest that there is expression of at least three mucins in MGH-U3 cells and that MAUB is a cancer-associated mucin distinct from those identified so far.