Tycko Benjamin, Li Chi-Ming, Buttyan Ralph
Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
Curr Mol Med. 2007 Aug;7(5):479-89. doi: 10.2174/156652407781387118.
Wnt/beta-catenin signaling is constitutively increased in several major classes of tumors arising from the urogenital tract. In this review we focus on this pathway mainly in Wilms tumors and prostate carcinomas, followed by a brief discussion of its potential role in other types of urological tumors. Molecular studies in these types of cancers have highlighted novel components upstream and downstream of this central oncogenic pathway. Beta-catenin gain-of-function mutations are strongly linked to WT1 loss-of-function mutations in syndromic Wilms tumors, and Wnt/beta-catenin signaling increases androgen receptor mRNA expression and blocks apoptosis in prostate cancers. Novel downstream target genes activated by Wnt/beta-catenin signaling are emerging from expression profiling in genetically defined classes of Wilms tumors, and similar analyses are expected to reveal additional downstream genes of this pathway specific to prostate cancers. The identities of these genes will likely suggest new targeted therapies for urological malignancies.
Wnt/β-连环蛋白信号通路在源自泌尿生殖道的几类主要肿瘤中持续增强。在本综述中，我们主要关注该通路在肾母细胞瘤和前列腺癌中的情况，随后简要讨论其在其他类型泌尿系统肿瘤中的潜在作用。这些类型癌症的分子研究突出了这一核心致癌通路上下游的新成分。在综合征性肾母细胞瘤中，β-连环蛋白功能获得性突变与WT1功能丧失性突变密切相关，并且Wnt/β-连环蛋白信号通路增加雄激素受体mRNA表达并阻断前列腺癌中的细胞凋亡。通过对基因定义的肾母细胞瘤类别进行表达谱分析，正在发现由Wnt/β-连环蛋白信号通路激活的新的下游靶基因，预计类似分析将揭示该通路中特定于前列腺癌的其他下游基因。这些基因的身份可能会为泌尿系统恶性肿瘤提示新的靶向治疗方法。
