Pilarsky C P, Schmidt U, Eissrich C, Stade J, Froschermaier S E, Haase M, Faller G, Kirchner T W, Wirth M P
Department of Urology, Technical University Dresden, Germany.
Prostate. 1998 Jul 1;36(2):85-91. doi: 10.1002/(sici)1097-0045(19980701)36:2<85::aid-pros3>3.0.co;2-d.
Prostate cancer (CaP) is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to identify genes related to the development of prostate cancer.
The RNA of 4 patients with untreated CaP was analyzed for differentially expressed genes. Using DD-PCR, we identified a downregulated cDNA-fragment in these prostate cancer cells. This fragment (N7) was cloned and further analyzed by CMRT-PCR, Northern-blot analysis, and in situ hybridization.
Sequence analysis revealed that N7 is identical to the 3'-untranslated region of the recently described immediate early gene Cyr61. Comparative multiplex RT-PCR with sequence specific primers showed that Cyr61 is downregulated in the tumor tissue of 7 out of 13 patients. By in situ hybridization we could demonstrate that the expression of Cyr61 is restricted to the epithelium of the prostate. Immunohistochemical analysis showed that Cyr61 protein could be found in the epithelium of normal prostatic tissue, whereas prostate cancer tissue showed a marked decrease of Cyr61 protein expression.
Cyr61 is a member of the emerging family of extracellular signaling proteins and enhances the effect of bFGF. The changed pattern of expression Cyr61 might therefore contribute to the altered interactions between epithelial and stromal cells in prostate carcinoma.
前列腺癌（CaP）是美国和欧洲最常见的肿瘤之一。我们使用差异显示PCR（DD-PCR）来鉴定与前列腺癌发生相关的基因。
分析4例未经治疗的CaP患者的RNA，以寻找差异表达基因。通过DD-PCR，我们在这些前列腺癌细胞中鉴定出一个下调的cDNA片段。该片段（N7）被克隆，并通过CMRT-PCR、Northern印迹分析和原位杂交进一步分析。
序列分析显示N7与最近描述的即时早期基因Cyr61的3'-非翻译区相同。用序列特异性引物进行的比较多重RT-PCR表明，13例患者中有7例肿瘤组织中Cyr61表达下调。通过原位杂交我们可以证明Cyr61的表达仅限于前列腺上皮。免疫组织化学分析表明，Cyr61蛋白可在正常前列腺组织上皮中发现，而前列腺癌组织中Cyr61蛋白表达明显降低。
Cyr61是新出现的细胞外信号蛋白家族的成员，可增强bFGF的作用。因此，Cyr61表达模式的改变可能导致前列腺癌上皮细胞与基质细胞之间相互作用的改变。
