A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells.
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.
Li
Tzu-Huey
TH
Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5328, USA.
Zhao
Hongjuan
H
Peng
Yue
Y
Beliakoff
Jason
J
Brooks
James D
JD
Sun
Zijie
Z
D000256:Adenoviridae / Q000235:genetics; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D013196:Dihydrotestosterone / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D059002:Androgen Receptor Antagonists; D000728:Androgens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone