δ-Catenin was identified initially as a neural specific protein that binds to the same juxtamembrane domain on classical cadherins as p120ctn, a tumor suppressor. Our recent analysis of the human genome revealed consistently an association of δ-catenin mRNA sequences with cells of cancerous origin, 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 Micro-Array revealed a close association of increased δ-catenin expression with human primary prostatic adenocarcinomas. The analyses of 180 human prostate cancer and benign prostate tissue samples demonstrated that an estimated 85% of prostatic adenocarcinomas showed an 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 p120ctn, 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 the reduced immunoreactivity for E-cadherin and p120ctn at the cell-cell junction. Therefore, δ-catenin overexpression may be intimately involved in regulating E-cadherin/p120ctn cell-cell adhesion in prostate cancer progression, and that a δ-catenin-E-cadherin-p120ctn cell junction cluster can be a useful panel of prostate cancer biomarkers.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]