promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells

• Published in: Nucleic acids research Vol. 35; no. 8; pp. 2767 - 2776
• Main Authors: Li, Tzu-Huey, Zhao, Hongjuan, Peng, Yue, Beliakoff, Jason, Brooks, James D, Sun, Zijie
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-04-2007; Oxford Publishing Limited (England)
• Subjects: Adenoviridae - genetics; Androgen Receptor Antagonists; Androgens - pharmacology; Animals; Cell Line, Tumor; Cell Proliferation; Dihydrotestosterone - pharmacology; Down-Regulation; Gene Expression Regulation; Male; Mice; Molecular Biology; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - metabolism; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptors, Androgen - metabolism; Receptors, Androgen - physiology; Transcriptional Activation - drug effects; Xenograft Model Antitumor Assays
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkm198

Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.