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Updated: Jun 27, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer
Gang Wang1, Jun Wang, Marianne D Sadar
1Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Abstract:
The androgen-signaling pathway plays an important role in the development and hormonal progression of prostate cancer to the castrate-resistant stage (also called androgen-independent or hormone refractory). The Wnt pathway and beta-catenin contribute to prostate biology and pathology. Here application of Affymetrix GeneChip analysis revealed the genomic similarity of the LNCaP hollow fiber model to clinical samples and identified genes with differential expression during hormonal progression. The fiber model samples clustered according to the expression profile of androgen-regulated genes to provide genomic evidence for the reactivation of the AR signaling pathway in castrate-resistant prostate cancer. Pathway-based characterization of gene expression identified activation of the Wnt pathway. Together with the increased expression of AR and beta-catenin, there was increased nuclear colocalization and interaction of endogenous AR and beta-catenin in castrate-resistant prostate cancer from castrated mice. Surprisingly, no interaction or colocalization of AR and beta-catenin could be detected in xenografts from noncastrated mice. These studies provide the first in vivo evidence to support aberrant activation of the AR through the Wnt/beta-catenin signaling pathway during progression of prostate cancer to the terminal castrate-resistant stage.
Insights
Prostate cancer progression to castrate-resistant stages involves androgen receptor (AR) and Wnt/beta-catenin pathway activation. This study shows in vivo evidence of AR and beta-catenin interaction in advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Androgen signaling pathway is crucial in prostate cancer (PC) development and progression.
- Castrate-resistant prostate cancer (CRPC) is a major challenge in PC treatment.
- Wnt pathway and beta-catenin are implicated in prostate biology and pathology.
Purpose of the Study:
- To investigate the genomic similarity of a prostate cancer hollow fiber model to clinical samples.
- To identify differentially expressed genes during hormonal progression of prostate cancer.
- To elucidate the role of Wnt/beta-catenin signaling in CRPC progression.
Main Methods:
- Affymetrix GeneChip analysis for gene expression profiling.
- Utilized LNCaP hollow fiber model and xenografts from castrated and noncastrated mice.
- Immunohistochemistry and Western blotting to assess protein expression and localization.
Main Results:
- Genomic similarity confirmed between the hollow fiber model and clinical samples.
- Identified differential gene expression during hormonal progression, supporting AR reactivation in CRPC.
- Demonstrated activation of the Wnt pathway and increased expression of AR and beta-catenin in CRPC.
- Observed nuclear colocalization and interaction of AR and beta-catenin in CRPC from castrated mice.
Conclusions:
- The study provides genomic evidence for AR signaling reactivation in CRPC.
- Aberrant activation of the androgen receptor (AR) via the Wnt/beta-catenin pathway is implicated in CRPC progression.
- This interaction is specific to the castrate-resistant state in vivo.
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