Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Int J Mol Med. 2011 Nov;28(5):799-807. doi: 10.3892/ijmm.2011.771. Epub 2011 Aug 10.
The role of the immune response in tumor progression, and disease outcome is still debated, and a lack of knowledge of the immune defenses in prostate cancer still exists. In addition, the ETS family of transcription factors which is involved in translocations frequently found in prostate cancer is reported to be essential for the regulation of immunity-related genes. In order to identify immunity-related genes in prostate cancer, we performed two microarrays using RNA extracted from laser microdissected glands of the normal prostate proper (or the peripheral zone) and moderately and poorly differentiated prostate carcinomas from patients who had undergone radical prostatectomy. Many differentially expressed genes were found, however, only immunity-related genes (B cell, innate, and T cell immunity) with an expression of more than 10-fold increase or decrease and a P<0.01 between the moderately differentiated tumors and the normal glands, and the poorly differentiated tumors and the normal glands were considered significant. Based on these two microarrays, we identified a set of 37 genes that were up- or down-regulated in tumors (moderately and poorly differentiated) compared to the normal glands. Analysis of these genes revealed, strikingly, that 31/37 of these genes have potential binding sites within their promoter regions for members of the ETS family of transcription factors, and some are reported to be targets of ETS members. These findings identified immunity-related genes in prostate cancer, and provided insights into their potential regulation, which may lead to a better early detection, immunotherapy, and therapeutic drug treatment of this disease. Unraveling the dynamics of the ETS-immunity-related genes will provide an invaluable insight into understanding prostate cancer immunology.
免疫反应在肿瘤进展和疾病结果中的作用仍存在争议，并且人们对前列腺癌中的免疫防御机制仍然知之甚少。此外，涉及前列腺癌中经常发现的易位的 ETS 转录因子家族被报道对于免疫相关基因的调节至关重要。为了鉴定前列腺癌中的免疫相关基因，我们使用从接受根治性前列腺切除术的患者的激光微切割正常前列腺固有腺体（或周围区）和中低度分化前列腺癌中提取的 RNA 进行了两个微阵列实验。发现了许多差异表达的基因，但是，只有免疫相关基因（B 细胞、先天和 T 细胞免疫）的表达增加或减少超过 10 倍，中度分化肿瘤与正常腺体之间以及低度分化肿瘤与正常腺体之间的 P<0.01 被认为是显著的。基于这两个微阵列，我们鉴定了一组 37 个在肿瘤（中低度分化）与正常腺体相比上调或下调的基因。这些基因的分析表明，这些基因中的 31/37 个基因在其启动子区域内具有 ETS 转录因子家族成员的潜在结合位点，并且一些基因被报道是 ETS 成员的靶标。这些发现鉴定了前列腺癌中的免疫相关基因，并深入了解了它们的潜在调节机制，这可能导致对这种疾病的早期检测、免疫疗法和治疗药物治疗的改善。揭示 ETS-免疫相关基因的动态将为深入了解前列腺癌免疫学提供宝贵的见解。
