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Formation of Human Prostate Epithelium Using Tissue Recombination of Rodent Urogenital Sinus Mesenchyme and Human Stem Cells
Published on: June 22, 2013
Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells
Raanan Berger1, Phillip G Febbo, Pradip K Majumder
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Abstract:
Androgen ablation is the primary treatment modality for patients with metastatic prostate cancer; however, the role of androgen receptor signaling in prostate cancer development remains enigmatic. Using a series of genetically defined immortalized and tumorigenic human prostate epithelial cells, we found that introduction of the androgen receptor induced differentiation of transformed prostate epithelial cells to a luminal phenotype reminiscent of organ-confined prostate cancer when placed in the prostate microenvironment. Moreover, androgen receptor expression converted previously androgen-independent, tumorigenic prostate epithelial cells into cells dependent on testosterone for tumor formation. These observations indicate that androgen receptor expression is oncogenic and addictive for the human prostate epithelium.
Insights
Androgen receptor expression is oncogenic in prostate cancer, driving tumor formation and dependence on testosterone. This finding clarifies the androgen receptor
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Androgen ablation is standard for metastatic prostate cancer.
- The precise role of androgen receptor (AR) signaling in prostate cancer initiation is unclear.
Purpose of the Study:
- To investigate the function of androgen receptor signaling in prostate cancer development.
- To determine if androgen receptor expression is oncogenic in human prostate epithelial cells.
Main Methods:
- Utilized genetically defined immortalized and tumorigenic human prostate epithelial cell lines.
- Introduced androgen receptor into these cells.
- Assessed cellular phenotype and tumor formation in a prostate microenvironment.
Main Results:
- Androgen receptor introduction induced differentiation of transformed cells to a luminal phenotype.
- Tumorigenic cells became testosterone-dependent for tumor formation upon AR expression.
- Androgen receptor expression was found to be oncogenic and create addiction to testosterone.
Conclusions:
- Androgen receptor signaling plays a critical oncogenic role in prostate cancer development.
- Prostate cancer cells can become addicted to testosterone through androgen receptor expression.
- Findings provide insight into prostate cancer pathogenesis and potential therapeutic targets.

