Nakaigawa N, Yao M, Kishida T, Kubota Y
Department of Urology, Yokohama City University School of Medicine.
Nihon Rinsho. 2001 Jan;59(1):104-9.
The oncogenic mechanisms of renal cell carcinoma(RCC) are becoming elucidated with recent advances in molecular biology. von Hipple-Lindau disease(VHL) tumor suppressor gene is mutated and inactivated frequently in clear cell type RCCs. The VHL protein forms a complex which shows a ubiquitin ligase activity. The lost of the ubiquitin ligase activity of VHL protein may be a key step for clear cell tumorigenesis. Papillary renal cell carcinomas are caused by activating mutation in the tyrosine kinase domain of the MET gene. This tumorigenic pathway is regulated by c-Src. Immunogene therapies have been started for the patients with advanced RCC. The information based on microarray and Serial Analysis of Gene Expression(SAGE) will provide novel diagnosis and therapy which focus on the tumorigenic mechanism of RCC in the near future.
随着分子生物学的最新进展,肾细胞癌(RCC)的致癌机制正逐渐被阐明。在透明细胞型肾细胞癌中,冯·希佩尔-林道病(VHL)肿瘤抑制基因经常发生突变并失活。VHL蛋白形成一种具有泛素连接酶活性的复合物。VHL蛋白泛素连接酶活性的丧失可能是透明细胞肿瘤发生的关键步骤。乳头状肾细胞癌是由MET基因酪氨酸激酶结构域的激活突变引起的。这种致癌途径受c-Src调节。针对晚期肾细胞癌患者的免疫基因治疗已经开始。基于微阵列和基因表达系列分析(SAGE)的信息将在不久的将来提供专注于肾细胞癌致癌机制的新诊断和治疗方法。