Harding Michael A, Theodorescu Dan
Department of Urology, University of Virginia, Charlottesville, VA 22908, USA.
Urol Oncol. 2007 Sep-Oct;25(5):401-6. doi: 10.1016/j.urolonc.2007.05.006.
The greatest risk for morbidity and mortality caused by bladder cancer is due to metastasis. For this reason, we have developed a paradigm for discovering the molecular mechanisms underlying bladder cancer progression to an invasive and metastatic phenotype. Results of microarray gene expression analysis of a cell culture model were parsed by identifying overlapping genes that correlate with increasing stage and grade of human tumors. One gene identified by this method, RhoGDI2, was tested in various in vitro and in vivo model systems and confirmed to be a metastasis suppressor gene. Using a similar strategy of gene identification by concordance of microarray gene expression results from cells expressing RhoGDI2 and human bladder cancers, two molecular effectors of RhoGDI2 signaling were identified. These targets, endothelin-1 and Neuromedin U are excellent potential targets for therapeutic intervention in the metastatic cascade.
膀胱癌导致发病和死亡的最大风险归因于转移。因此，我们开发了一种范式，用于发现膀胱癌进展为侵袭性和转移表型的分子机制。通过识别与人类肿瘤分期和分级增加相关的重叠基因，对细胞培养模型的微阵列基因表达分析结果进行了解析。通过这种方法鉴定出的一个基因RhoGDI2，在各种体外和体内模型系统中进行了测试，并被证实是一种转移抑制基因。利用与表达RhoGDI2的细胞和人类膀胱癌的微阵列基因表达结果一致性进行基因鉴定的类似策略，确定了RhoGDI2信号传导的两个分子效应器。这些靶点，内皮素-1和神经介素U，是转移级联治疗干预的极佳潜在靶点。
