Journal
CANCER RESEARCH
Volume 69, Issue 18, Pages 7165-7169Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-1448
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Funding
- Patrick C. Walsh Prostate Cancer Research Fund Virginia
- Warren Schwerin Scholarship
- Department of Defense Prostate Cancer Research Fund [W81XWH-08-1-0156]
- Departament d' Universitats, Recerea i Societal de la Informacio de la Generalitat de Catalunya (Catalunya, Spain)
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Androgen receptor (AR)-mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (Cap) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced Cap tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in Cap when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to Cap pathogenesis. [Cancer Res 2009;69(18):7165-9]
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