High expression of a new marker PCA-1 in human prostate carcinoma
High expression of a new marker PCA-1 in human prostate carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-05-0195
复制
发表时间：
2005-07-15
影响因子：
11.5
通讯作者：
Tsujikawa, K
中科院分区：
文献类型：
--
作者：
Konishi, N;Nakamura, M;Tsujikawa, K
目的：确定前列腺癌发生的遗传因素是关键。新的癌症特异性标志物有助于早期检测，区分癌症和非恶性疾病，并监测前列腺疾病的临床。因此，我们研究差异基因显示，试图找出可能参与前列腺癌的基因。实验设计：应用荧光差异显示分析人类前列腺癌，我们已经确定并克隆了几个c DNA转录本。针对合成肽产生抗血清，并用于Western印迹和免疫组织化学分析。还通过实时逆转录PCR分析了它们的RNA。对于功能分析，我们评估了甲基甲烷磺酸盐（MMS）诱导的毒性COS-7细胞cDNA transfection.Results后：我们确定了一个基因，指定的前列腺癌抗原-1（Pca-1），这表明在前列腺癌的高mRNA表达。PCA-1的氨基酸序列与大肠杆菌AlkB（一种DNA烷基化损伤修复酶）的氨基酸序列高度相似。通过免疫组化分析，PCA-1在大量的前列腺癌样本和高级别前列腺上皮内瘤变的非典型细胞中表达，但在良性前列腺增生或正常邻近组织中不表达。PCA-1转染的COS-7细胞对MMS诱导的细胞死亡有较强的抵抗力。结论：PCA-1可能是一种有用的诊断标志物。此外，由于这种AlkB的人类对应物在哺乳动物细胞中表现出对烷基化损伤的保护功能，PCA-1也可以作为前列腺癌的治疗靶分子。
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 maybe involved in prostate carcinogenesis.Experimental Design: Applying fluorescent differential display analysis to human prostate carcinomas, we have identified and cloned several c DNA transcripts. Antisera were raised against synthetic peptides and used in Western blot and immunohistochemical analyses. Them RNAs 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.