Purpose: Identifying the genetic factors involved in prostate carcinogenesis is critical. Novel cancer-specific markers aid in early detection, in differentiating between cancer and nonmalignant disorders, and in monitoring clinical of prostate disease. We therefore examined differential gene displays in an attempt to identify genes that may be involved in prostate carcinogenesis.
Experimental design: Applying fluorescent differential display analysis to human prostate carcinomas, we have identified and cloned several cDNA transcripts. Antisera were raised against synthetic peptides and used in Western blot and immunohistochemical analyses. The mRNAs were also analyzed by real-time reverse transcription-PCR. For functional analysis, we assessed methylmethane sulfonate (MMS)-induced toxicity in COS-7 cells after cDNA transfection.
Results: We identified a gene, designated prostate cancer antigen-1 (pca-1), which shows high mRNA expression in prostate carcinoma. Database analysis of the deduced amino acid sequence of PCA-1 indicated high similarity to Escherichia coli AlkB, a DNA alkylation damage repair enzyme. By immunohistochemical analysis, PCA-1 was expressed in a high number of both prostate carcinoma samples and in the atypical cells within high-grade prostatic intraepithelial neoplasias but not in benign prostatic hyperplasia or normal adjacent tissues. PCA-1-transfected COS-7 cells further showed resistance against MMS-induced cell death.
Conclusions: 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.