Repression of the Androgen Receptor by WT1, a Tumor Suppressor Gene
Abstract
The androgen pathway is central to prostate tumorigenesis. An increased risk of higher stage, more aggressive prostate cancer is associated with a more active androgen receptor (AR). We are investigating an innovative transcription based mechanism that represses AR activity in vitro: Our hypothesis is that the tumor suppressor gene, WTI, may play a role in prostate tumorigenesis mediated by repression of AR gene expression. To validate our AR promoter data we demonstrated that AR target gene down-regulation by WTI is dependent on an intact DNA binding domain, is mediated by AR and is hormone dependent. Additionally we confirmed our RNA studies showing that WTI protein expression patterns are inversely related to AR expression. Androgen responsive cell lines express AR but fail to express WTI, while androgen independent lines express WTI and lack AR, suggesting a correlation with late-stage androgen independence. Recently we established stable transfected tumor cell lines and are now determining their growth characteristics with the intent of using them to establish a mouse model of prostate cancer progression. With the correlation of WTI expression with higher-grade disease and the potential to demonstrate WTI repression of AR expression in mice, we will establish the role of WTI in the development of androgen independence.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADB257105
Entities
People
- Gail C. Fraizer
Organizations
- The University of Texas MD Anderson Cancer Center