Savinainen K J, Linja M J, Saramäki O R, Tammela T L J, Chang G T G, Brinkmann A O, Visakorpi T
Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, FIN-33014 Tampere, Finland.
Br J Cancer. 2004 Mar 8;90(5):1041-6. doi: 10.1038/sj.bjc.6601648.
The long arm of chromosome 8 is one of the most common regions of amplification in cancers of several organs, especially carcinomas of the breast and prostate. TRPS1, MYC and EIF3S3 genes are located in one of the minimal regions of amplification, 8q23-q24, and have been suggested to be the target genes of the amplification. Here, our goal was to study copy number and expression of the three genes in order to investigate the significance of the genes in breast and prostate cancer. By using fluorescence in situ hybridisation (FISH), we first found that TRPS1 and EIF3S3 were amplified together in about one-third of hormone-refractory prostate carcinomas. Next, we analysed the mRNA expression of the three genes by real-time quantitative RT-PCR and the gene copy number by FISH in six breast and five prostate cancer cell lines. Breast cancer cell line, SK-Br-3, which contained the highest copy number of all three genes, showed overexpression of only EIF3S3. Finally, the expression levels of TRPS1, EIF3S3 and MYC were measured in freshly frozen clinical samples of benign prostate hyperplasia (BPH), as well as untreated and hormone-refractory prostate carcinoma. The TRPS1 and MYC expression levels were similar in all prostate tumour groups, whereas EIF3S3 expression was higher (P=0.029) in prostate carcinomas compared to BPH. The data suggest that the expression of EIF3S3 is increased in prostate cancer, and that one of the mechanisms underlying the overexpression is the amplification of the gene.
8号染色体长臂是多个器官癌症中最常见的扩增区域之一，尤其是乳腺癌和前列腺癌。TRPS1、MYC和EIF3S3基因位于最小扩增区域之一8q23 - q24，被认为是扩增的靶基因。在此，我们的目标是研究这三个基因的拷贝数和表达情况，以探讨这些基因在乳腺癌和前列腺癌中的意义。通过荧光原位杂交（FISH），我们首先发现约三分之一的激素难治性前列腺癌中TRPS1和EIF3S3共同扩增。接下来，我们通过实时定量RT - PCR分析了这三个基因的mRNA表达，并通过FISH分析了六种乳腺癌和五种前列腺癌细胞系中的基因拷贝数。乳腺癌细胞系SK - Br - 3含有所有三个基因的最高拷贝数，但仅EIF3S3过表达。最后，我们在良性前列腺增生（BPH）以及未经治疗和激素难治性前列腺癌的新鲜冷冻临床样本中测量了TRPS1、EIF3S3和MYC的表达水平。所有前列腺肿瘤组中TRPS1和MYC的表达水平相似，而与BPH相比，前列腺癌中EIF3S3的表达更高（P = 0.029）。数据表明前列腺癌中EIF3S3的表达增加，且过表达的潜在机制之一是该基因的扩增。
