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Series GSE13919 Query DataSets for GSE13919
Status Public on Mar 17, 2009
Title A Novel Androgen Receptor Splice Variant Is Upregulated during Prostate Cancer Progression
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The androgen receptor (AR) plays a key role in progression to incurable androgen-ablation resistant prostate cancer (PCA). We have identified three novel AR splice variants lacking the ligand binding domain (designated as AR3, AR4 and AR5) in hormone insensitive PCA cells. AR3, one of the major splice variants expressed in human prostate tissues, is constitutively active and its transcriptional activity is not regulated by androgens or antiandrogens. Immunohistochemistry analysis on tissue microarrays containing 429 human prostate tissue samples shows that AR3 is significantly upregulated during PCA progression and AR3 expression level is correlated with the risk of tumor recurrence after radical prostatectomy. Overexpression of AR3 confers ablation-independent growth of PCA cells while specific knock-down of AR3 expression (without altering AR level) in hormone resistant PCA cells attenuates their growth under androgen-depleted conditions in both cell culture and xenograft models, suggesting an indispensable role of AR3 in ablation-independent growth of PCA cells. Furthermore, AR3 may play a distinct yet essential role in ablation-independent growth through regulating a unique set of genes including AKT1, which are not regulated by the prototype AR. Our data suggest that aberrant expression of AR splice variants may be a novel mechanism underlying ablation-independence during PCA progression and AR3 may serve as a prognostic marker to predict patient outcome in response to hormonal therapy. Given that these novel AR splice variants are not inhibited by currently available anti-androgen drugs, development of new drugs targeting these AR isoforms may potentially be effective for treatment of ablation-resistant PCA.
Overall design Total RNA was extracted from CWR-R1 and 22Rv1 cells treated with shAR3-1, shARa and the scrambled shRNA control, respectively. Each of CWR-R1 and 22Rv1 cells treated with shAR3-1 was compared with the scrambled shRNA control. The same experiments were performed for the cells treated with shARa.
Citation(s) 19244107
Submission date Dec 11, 2008
Last update date Feb 22, 2018
Contact name Hegang Chen
Organization name University of Maryland School of Medicine
Street address 660 West Redwood Street
City Baltimore
State/province MD
ZIP/Postal code 21201
Country USA
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (4)
GSM350620 AR3_Control_22Rv1
GSM350621 AR3_Control_CWR_R1
GSM350622 AR_Control_22Rv1
BioProject PRJNA110343

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE13919_RAW.tar 63.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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