The Wnt/Beta-Catenin Pathway in Wilms Tumors and Prostate Cancers

Benjamin Tycko; Chi-Ming Li; Ralph Buttyan

Abstract

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.

Keywords: Wilms tumor, kidney development, prostate cancer, Wnt, beta-catenin, WT1, androgen receptor, urological tumors