Increased expression of delta-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer.
delta-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 delta-catenin messenger RNA sequences with malignant cells, although the significance of these findings was unclear. In this study, we report that a number of delta-catenin epitopes were expressed in human prostate cancer cells. Western blot and tissue microarray revealed a close association between increased delta-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 delta-catenin immunoreactivity. delta-Catenin expression increased with prognostically significant increased Gleason scores. By analyzing the same tumor cell clusters using consecutive sections, we showed that an increased delta-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 delta-catenin in tumorigenic CWR-R1 cells that are derived from human prostate cancer xenograft resulted in reduced immunoreactivity for E-cadherin and p120ctn at the cell-cell junction. This is the first study comparing overexpression of delta-catenin with the E-cadherin/catenin system in cancer and shows that delta-catenin may be intimately involved in regulating E-cadherin/p120ctn cell-cell adhesion in prostate cancer progression.
Lu
Qun
Q
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. luq@mail.ecu.edu
Dobbs
Larry J
LJ
Gregory
Christopher W
CW
Lanford
George W
GW
Revelo
Monica P
MP
Shappell
Scott
S
Chen
Yan-hua
YH
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D011379:Prognosis; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011863:Radioimmunoassay; D051381:Rats; D017154:Stromal Cells / Q000166:cytology; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D000939:Epitopes; D010750:Phosphoproteins; D049452:Green Fluorescent Proteins; D000095002:Delta Catenin