Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening Journal Article
| Authors: | Dahlman, K. B.; Parker, J. S.; Shamu, T.; Hieronymus, H.; Chapinski, C.; Carver, B.; Chang, K.; Hannon, G. J.; Sawyers, C. L. |
| Article Title: | Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening |
| Abstract: | There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets. © 2012 Dahlman et al. |
| Keywords: | controlled study; unclassified drug; human cell; genetics; cell proliferation; reproducibility; reproducibility of results; metabolism; cell death; gene; cell survival; apoptosis; protein; small interfering rna; rna, small interfering; recurrence; rna interference; drug effect; pathology; cell line, tumor; prostate cancer; prostatic neoplasms; microarray analysis; cancer cell; prostate tumor; tumor cell line; androgen antagonists; recurrent disease; androgen receptor; validity; antiandrogen; bicalutamide; tumor gene; short hairpin rna; anilides; nitriles; tosyl compounds; nitrile; anilide; toluenesulfonic acid derivative; genetic identification; akt1 gene; molecularly targeted therapy; genes, neoplasm; molecular targeted therapy; nucleic acid database; databases, nucleic acid; akt1 protein; psmc1 protein; strada protein; tik protein; psmc1 gene; strada gene; tik gene |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e34414 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0034414 |
| PROVIDER: | scopus |
| PMCID: | PMC3324507 |
| PUBMED: | 22509301 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "Source: Scopus" |
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