P-CADHERIN IS A BASAL CELL-SPECIFIC EPITHELIAL MARKER THAT IS NOT EXPRESSED IN PROSTATE-CANCER

P-Cadherin is a member of the cadherin family of cell surface glycopro teins that mediate Ca2+-dependent cell-cell adhesion and is expressed in a differential fashion in normal epithelial tissues, The expression of P-cadherin in human prostate cancer development has not been inves tigated previously, By immunohistochemistry, we show that P-cadherin e xpression is restricted to the cell-cell border of basal epithelial ce lls in 30 normal prostate samples, This staining is down-regulated in prostatic intraepithelial neoplasia and is absent in all 25 of the wel l to poorly differentiated prostate cancer specimens analyzed, To exam ine potential P-cadherin-regulatory elements, we sequenced the 5'-flan king region of this gene. Similar to the mouse gene, the human P-cadhe rin promoter is TATA-less, contains an Sp-l binding site and, analogou s to the human E-cadherin sequence, demonstrates a GC-rich region char acteristic of a CpG island, Cytosine methylation of this region occurs in P-cadherin-negative prostate cancer cell lines but not in cell lin es expressing this gene, In vivo, a lack of expression in 12 clinical prostate cancer specimens is not associated with methylation of the P- cadherin promoter, These results demonstrate that the expression of th e basal cell marker P-cadherin is lost in prostate cancer development and that in vivo mechanisms other than cytosine methylation regulate t his consistent loss of expression.