Genomics

Dataset Information

299

The cistrome and transcriptome landscape of androgen receptor splice variants in castration-resistant prostate cancer cells


ABSTRACT: The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress. Androgen receptor (AR) binding sites in human prostate cancer 22Rv1 cell lines were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.

ORGANISM(S): Homo sapiens  

SUBMITTER: Donald Tindall   Liguo Wang  Ji Lu  LIGUO WANG 

PROVIDER: E-GEOD-58478 | ArrayExpress | 2014-09-10

SECONDARY ACCESSION(S): SRP043210GSE58478PRJNA252725

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

The cistrome and gene signature of androgen receptor splice variants in castration resistant prostate cancer cells.

Lu Ji J   Lonergan Peter E PE   Nacusi Lucas P LP   Wang Liguo L   Schmidt Lucy J LJ   Sun Zhifu Z   Van der Steen Travis T   Boorjian Stephen A SA   Kosari Farhad F   Vasmatzis George G   Klee George G GG   Balk Steven P SP   Huang Haojie H   Wang Chunxi C   Tindall Donald J DJ  

The Journal of urology 20140814 2


Spliced variant forms of androgen receptor were recently identified in castration resistant prostate cancer cell lines and clinical samples. We identified the cistrome and gene signature of androgen receptor splice variants in castration resistant prostate cancer cell lines and determined the clinical significance of androgen receptor splice variant regulated genes.The castration resistant prostate cancer cell line 22Rv1, which expresses full-length androgen receptor and androgen receptor splice  ...[more]

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