Aberrant cadherin expression in bladder carcinoma cells

Altered E-cadherin expression is frequently observed in late-stage bladder cancer and is associated with a poor prognosis. Although loss of E-cadherin has been identified in 5 of 15 bladder carcinoma cell lines, the continued membrane localization of catenins in these cells suggested the expression of alternative cadherin members. Immunoprecipitation of beta-catenin from r adiolabeled cell lysates revealed coprecipitation of a 130-kD protein in ce ll lines lacking E-cadherin, In Western blot analysis, this putative cadher in member was found not to be P-cadherin but was immunologically related to cadherins, as revealed by reprobing of the blots with a pan-cadherin antib ody. Using RT-PCR with degenerate primers targeted to a highly conserved C- terminal region of classical cadherins, we identified six cadherin members in E-cadherin-negative cells, These proteins were P- and N-cadherin, cadher in-4, cadherin-6, cadherin-8, and a novel cadherin, designated BT-1, which showed significant homology with the mouse T1-cadherin, Because N-cadherin was the most abundant sequence isolated, we confirmed expression of this pr otein in Western blots of cell lines and tumor lysates, Bladder cell lines lacking E- or P-cadherin showed catenin-complexed N-cadherin in all cases, Membrane localization of N-cadherin was demonstrated by immunofluorescence of cells and bladder tumor tissue. Because N-cadherin was identified in inv asive bladder carcinoma cells, it is unlikely that this cadherin member pla ys an invasion-suppressor role.