High Expression of a New Marker PCA-1 in Human Prostate Carcinoma

Abstract

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 inWestern 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-1may also serve as a therapeutic target molecule for prostate cancer.

Damage of DNA and proteins by major lipid peroxidation products in genome stability

“…This could suggest that apart from the BER system, ethenoadducts are eliminated from DNA by other repair activities, Their level was significantly increased in some types of cancer e.g. prostate cancer [100,101] however their contribution to repair of exocyclic DNA adducts in mammals still is not clear.…”

The role of HRK gene in human cancer

“…Various studies have been performed investigating the genetic factors related to prostate carcinogenesis (Konishi et al, 2005a(Konishi et al, , b, 2008, but as yet, critical specific molecular markers that clearly identify malignant potential have not been found. Apoptosis regulators play one of the most critical roles in tumorigenesis, and an imbalance between cell proliferation and apoptosis contributes to tumor progression (Steinbach et al, 2002;Debatin et al, 2003).…”

HRK inactivation associated with promoter methylation and LOH in prostate cancer

“…The details of the IHC procedure have been described previously [16,19], but briefly, deparaffinized sections were heated to boiling for 5 min in a 10 mM sodium citrate (pH 6.0) buffer in a pressure cooker, then incubated overnight at 48C with antibodies at a dilution of 1:200. Binding reactions were visualized using a Histofine SAB-PO kit and diaminobenzidine (Nichirei, Tokyo, Japan) with hematoxylin counterstaining.…”