Identification and expression of the oxidative demethylase PCA‐1 in prostate cancer

Prostate carcinoma is the most common malignancy in men and the second leading cause of cancer death in Western countries. In searching for potential gene markers for prostate carcinoma, we have studied the molecular identification relating to the gene expression between prostate carcinomas and normal adjacent tissues using fluorescent differential display analysis. In the process, we have identified a new gene designated as prostate cancer antigen‐1 (PCA‐1), which showed increased mRNA expression in cancer tissues compared with normal or non‐cancerous adjacent tissues. By homology search, PCA‐1 was found to have high similarity to an E. coli DNA alkylation damage repair enzyme AlkB. Immunohistochemical analysis using anti‐PCA‐1 antisera indicated that PCA‐1 is highly expressed in human prostate cancer as well as high‐grade intraepithelial neoplasia region, but not in normal prostatic gland or benign prostatic hyperplasia. PCA‐1 cDNA transfection rescued cell death of COS‐7 cells exposed with methylmethane sulfonate. These findings suggest that PCA‐1 could be a useful diagnostic marker. Furthermore, because this human counterpart of AlkB exhibits a protective function against alkylation damage in mammalian cells, PCA‐1 may also serve as a therapeutic target molecule for prostate cancer. This study was supported by Grants‐in‐Aid for Cancer Research form the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant of LRI by JCIA