Bull J H, Ellison G, Patel A, Muir G, Walker M, Underwood M, Khan F, Paskins L
Enabling Science and Technology, AstraZeneca, Cheshire, SK10 4TG, UK.
Br J Cancer. 2001 Jun 1;84(11):1512-9. doi: 10.1054/bjoc.2001.1816.
The identification of novel genes or groups of genes expressed in prostate cancer may allow earlier diagnosis or more accurate staging of the disease. We describe the assembly and use of a 1877-member microarray representing cDNA clones from a range of prostate cancer stages and grades, precursor lesions and normal tissue. Using labelled cDNA from tumour samples obtained from TURP or radical prostatectomy, analysis of expression patterns identified many up-regulated transcripts. Cell lines were found to over-express fewer genes than diseased tissue samples. 17 known genes were found to over-express more than 4-fold in 4 or more cancers out of 15 cancers. Only 2 genes were over-expressed in 6 out of 15 cancers or more, whilst no genes were consistently found to be over-expressed in all cancer samples. Novel prostate cancer associations for several well characterized genes or full length cDNAs were identified, including PLRP1, JM27, human UbcM2, dynein light intermediate chain 2 and human homologue of rat sec61. Novel associations with high-grade PIN include: breast carcinoma fatty acid synthase and cDNA DKFZp434B0335. We shortlist and discuss the most significant over-expressed genes in prostate cancer and PIN, and highlight expression differences between malignant and benign samples.
鉴定前列腺癌中表达的新基因或基因群,可能有助于对该疾病进行更早的诊断或更准确的分期。我们描述了一个包含1877个成员的微阵列的组装和使用情况,该微阵列代表了来自一系列前列腺癌阶段和分级、前驱病变及正常组织的cDNA克隆。使用来自经尿道前列腺切除术(TURP)或根治性前列腺切除术获取的肿瘤样本的标记cDNA,对表达模式的分析鉴定出许多上调的转录本。发现细胞系中过表达的基因比患病组织样本中的少。在15种癌症中的4种或更多癌症中,发现有17个已知基因的过表达超过4倍。在15种癌症中的6种或更多癌症中,只有2个基因过表达,而在所有癌症样本中未发现始终过表达的基因。鉴定出了几种特征明确的基因或全长cDNA与前列腺癌的新关联,包括PLRP1、JM27、人UbcM2、动力蛋白轻中间链2以及大鼠sec61的人同源物。与高级别前列腺上皮内瘤变(PIN)的新关联包括:乳腺癌脂肪酸合酶和cDNA DKFZp434B0335。我们筛选并讨论了前列腺癌和PIN中最显著的过表达基因,并突出了恶性和良性样本之间的表达差异。