Increased expression of δ-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer

Summary δ -Catenin, or neural plakophilin-related armadillo protein, is a unique armadillo domain-containing protein in that it is neural-specific and primarily expressed in the brain. However, our recent analysis of the human genome revealed a consistent association of δ-catenin messenger RNA sequences with malignant cells, although the significance of these findings was unclear. In this study, we report that a number of δ -catenin epitopes were expressed in human prostate cancer cells. Western blot and tissue microarray revealed a close association between increased δ -catenin expression and human primary prostatic adenocarcinomas. The analyses of 90 human prostate cancer and 90 benign prostate tissue samples demonstrated that an estimated 85% of prostatic adenocarcinomas showed enhanced δ -catenin immunoreactivity. δ -Catenin expression increased with prognostically significant increased Gleason scores. By analyzing the same tumor cell clusters using consecutive sections, we showed that an increased δ -catenin immunoreactivity was accompanied by the down-regulation and redistribution of E-cadherin and p120 ctn , major cell junction proteins whose inactivation is frequently associated with cancer progression. Furthermore, overexpression of δ -catenin in tumorigenic CWR-R1 cells that are derived from human prostate cancer xenograft resulted in reduced immunoreactivity for E-cadherin and p120 ctn at the cell-cell junction. This is the first study comparing overexpression of δ -catenin with the E-cadherin/catenin system in cancer and shows that δ -catenin may be intimately involved in regulating E-cadherin/p120 ctn cell-cell adhesion in prostate cancer progression.