Analysis of human prostate century by fluorescent differential display

前列腺癌的发生有许多遗传学改变，但很难将这些分子知识转化为广泛适用于疾病管理和治疗的诊断和预后标准。最近的分子研究已经证实了几个在遗传性前列腺癌中重要的候选基因；然而，目前还没有发现这种肿瘤的特异性分子标记。在寻找前列腺癌潜在基因标记物的过程中，我们利用荧光差异显示(FDD)分析，探索了与肿瘤基因表达模式相关的分子图谱。我们已经确定了一个新的基因，命名为前列腺癌抗原-1(PCA-1)，它在前列腺癌中表达增加。通过CDNA末端的快速扩增，克隆出与PCR产物相对应的全长转录本。对推导的氨基酸序列的分析表明，该基因编码一种新的50kDA的推定蛋白，免疫组织化学在许多前列腺癌(63/70；90%)以及高级别前列腺上皮内瘤变的非典型细胞中表达。Western印迹分析表明，PCA-1在前列腺癌PC-3和DU 145中也有上调，但在LNCaP中没有上调。其他人类癌症，如甲状腺癌、胃癌、肺癌、乳腺癌和肾癌，PCA-1被证明为阴性，这表明前列腺癌具有特异性。虽然免疫反应性与组织学肿瘤分级或病理分期无明显相关性，但该基因可能与肿瘤发生的早期阶段有关，因此可作为前列腺癌的诊断和治疗工具。

A number of genetic changes have been shown to occur in prostate tumorigenesis, yet it is difficult to translate this molecular knowledge into diagnostic and prognostic criteriae widely applicable for the management and treatment of the disease. Recent molecular studies have demonstrated several candidate genes important in hereditary prostate cancer; however, no specific molecular marker for this tumor has as yet been found. In searching for potential gene markers for prostate carcinoma, we explored the molecular profile relating to the gene expression patterns in tumors using fluorescent differential display (FDD) analysis. We have identified a novel gene, designated prostate cancer antigen-1 (PCA-1), which shows increased expression in prostate carcinoma. The full-length transcript corresponding to the PCR product was cloned by rapid amplification of CDNA ends. Analysis of the deduced amino acid sequence demonstrated that this gene encodes a novel 50-Kda putative protein immunohistochemically expressed in a high number of prostate carcinomas (63/70; 90%) as well as in the atypical cells in high-grade prostatic intraepithelial neoplasias. Western blot analysis indicates that PCA-1 is also up-regulated in prostate cancer cell lines PC-3 and DU 145, but not in LNCaP Other human cancers, such as thyroid, gastric colorectal, lung, breast, and renal cell cancers, proved negative for PCA-1 , indicating specificity for prostatic lesions. Although there appears to be no significant correlation between immunoreactivity and histological tumor grade or pathological stage, the gene may be relevant to the early stages of the tumor development, thus making it useful as a diagnostic and therapeutic tool for dealing with prostate cancer.