Prostate cancer antigen‐1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer

Abstract

A novel gene, prostate cancer antigen (PCA)‐1, was recently reported to be expressed in the prostate; however, its biological roles remain unclear. Knockdown of the PCA‐1 gene by small interfering RNA transfection induced apoptosis through reducing the expression of the anti‐apoptotic molecule Bcl‐xl and cytoplasmic release of cytochrome c in the androgen‐independent prostate cancer cell line PC3. Moreover, in vitro matrigel and in vivo chorioallantoic membrane assays showed that silencing of PCA‐1 significantly downregulated discoidin receptor (DDR)‐1 expression, resulting in suppression of cancer‐cell invasion. Transfection with PCA‐1 increased the levels of both Bcl‐xl and DDR1, which made the cells more invasive through the upregulation of matrix metalloproteinase 9 in DU145. Interestingly, long‐term culture using androgen‐free medium increased the level of PCA‐1 and the related expression of Bcl‐xl and DDR‐1 in the androgen‐sensitive cancer cell line LNCaP, suggesting that PCA‐1 signaling is associated with androgen independence. Immunohistochemical analysis in a series of 169 prostate carcinomas showed that PCA‐1 and DDR1 were strongly expressed in prostate cancer cells, including preneoplastic lesions, but there was little or no expression in normal epithelium. Moreover, the expression of PCA‐1 and DDR‐1 was associated with a hormone‐independent state of prostate cancer. Taken together, we propose that PCA‐1–DDR‐1 signaling is a new important axis involved in malignant potential prostate cancer associated with hormone‐refractory status. (Cancer Sci 2008; 99: 39–45)