Bussemakers M J, van Bokhoven A, Verhaegh G W, Smit F P, Karthaus H F, Schalken J A, Debruyne F M, Ru N, Isaacs W B
Urology Research Laboratory, University Hospital Nijmegen, The Netherlands.
Cancer Res. 1999 Dec 1;59(23):5975-9.
Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the Western male population. Despite the tremendous efforts that have been made to improve the early detection of this disease and to design new treatment modalities, there is still an urgent need for new markers and therapeutic targets for the management of prostate cancer patients. Using differential display analysis to compare the mRNA expression patterns of normal versus tumor tissue of the human prostate, we identified a cDNA, DD3, which is highly overexpressed in 53 of 56 prostatic tumors in comparison to nonneoplastic prostatic tissue of the same patients. Reverse transcription-PCR analysis using DD3-specific primers indicated that the expression of DD3 is very prostate specific because no product could be amplified in 18 different normal human tissues studied. Also, in a sampling of other tumor types and a large number of cell lines, no expression of DD3 could be detected. Molecular characterization of the DD3 transcription unit revealed that alternative splicing and alternative polyadenylation occur. The fact that no extensive open reading frame could be found suggests that DD3 may function as a noncoding RNA. The DD3 gene was mapped to chromosome 9q21-22, and no homology of DD3 to any gene present in the computer databases was found. Our data indicate that DD3 is one of the most prostate cancer-specific genes yet described, and this makes DD3 a promising marker for the early diagnosis of prostate cancer and provides a powerful tool for the development of new treatment strategies for prostate cancer patients.
前列腺癌是西方男性人群中最常被诊断出的恶性肿瘤，也是癌症相关死亡的第二大主要原因。尽管在改善该疾病的早期检测以及设计新的治疗方式方面已经付出了巨大努力，但对于前列腺癌患者的管理而言，仍然迫切需要新的标志物和治疗靶点。通过差异显示分析比较人类前列腺正常组织与肿瘤组织的mRNA表达模式，我们鉴定出一个cDNA，即DD3，与同一患者的非肿瘤性前列腺组织相比，它在56例前列腺肿瘤中的53例中高度过表达。使用DD3特异性引物进行的逆转录-聚合酶链反应分析表明，DD3的表达具有非常高的前列腺特异性，因为在所研究 的18种不同人类正常组织中均未扩增出产物。此外，在其他肿瘤类型的样本以及大量细胞系中，均未检测到DD3的表达。DD3转录单元的分子特征显示存在可变剪接和可变聚腺苷酸化。未发现广泛开放阅读框这一事实表明DD3可能作为非编码RNA发挥作用。DD3基因被定位到9号染色体q21-22区域，并且未发现DD3与计算机数据库中任何基因具有同源性。我们的数据表明，DD3是迄今所描述的最具前列腺癌特异性的基因之一，这使得DD3成为前列腺癌早期诊断的一个有前景的标志物，并为前列腺癌患者新治疗策略的开发提供了一个有力工具。
