Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines

Honglin Chen, Stephen J. Libertini, Michael George, Satya Dandekar, Clifford G. Tepper, Bushra Al-Bataina, Hsing Jien Kung, Paramita M. Ghosh, Maria Mudryj

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Prostate carcinoma (CaP) is a heterogeneous multifocal disease where gene expression and regulation are altered not only with disease progression but also between metastatic lesions. The androgen receptor (AR) regulates the growth of metastatic CaPs; however, sensitivity to androgen ablation is short lived, yielding to emergence of castrate-resistant CaP (CRCaP). CRCaP prostate cancers continue to express the AR, a pivotal prostate regulator, but it is not known whether the AR targets similar or different genes in different castrate-resistant cells. In this study, we investigated AR binding and AR-dependent transcription in two related castrate-resistant cell lines derived from androgen-dependent CWR22-relapsed tumors: CWR22Rv1 (Rv1) and CWR-R1 (R1). Expression microarray analysis revealed that R1 and Rv1 cells had significantly different gene expression profiles individually and in response to androgen. In contrast, AR chromatin immunoprecipitation (ChIP) combined with promoter DNA microarrays (ChIP-on-chip) studies showed that they have a similar AR-binding profile. Coupling of the microarray study with ChIP-on-chip analysis identified direct AR targets. The most prominent function of transcripts that were direct AR targets was transcriptional regulation, although only one transcriptional regulator, CCAAT/enhancer binding protein δ, was commonly regulated in both lines. Our results indicate that the AR regulates the expression of different transcripts in the two lines, and demonstrate the versatility of the AR-regulated gene expression program in prostate tumors.

Original languageEnglish
Pages (from-to)857-873
Number of pages17
JournalEndocrine-Related Cancer
Volume17
Issue number4
DOIs
Publication statusPublished - Dec 1 2010
Externally publishedYes

Fingerprint

Androgen Receptors
Prostatic Neoplasms
Genome
Cell Line
Genes
Chromatin Immunoprecipitation
Androgens
Prostate
CCAAT-Enhancer-Binding Proteins
Gene Expression Regulation
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Transcriptome
Disease Progression
Neoplasms
Carcinoma
Gene Expression

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Cite this

Chen, H., Libertini, S. J., George, M., Dandekar, S., Tepper, C. G., Al-Bataina, B., ... Mudryj, M. (2010). Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. Endocrine-Related Cancer, 17(4), 857-873. https://doi.org/10.1677/ERC-10-0081

Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. / Chen, Honglin; Libertini, Stephen J.; George, Michael; Dandekar, Satya; Tepper, Clifford G.; Al-Bataina, Bushra; Kung, Hsing Jien; Ghosh, Paramita M.; Mudryj, Maria.

In: Endocrine-Related Cancer, Vol. 17, No. 4, 01.12.2010, p. 857-873.

Research output: Contribution to journalArticle

Chen, H, Libertini, SJ, George, M, Dandekar, S, Tepper, CG, Al-Bataina, B, Kung, HJ, Ghosh, PM & Mudryj, M 2010, 'Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines', Endocrine-Related Cancer, vol. 17, no. 4, pp. 857-873. https://doi.org/10.1677/ERC-10-0081
Chen, Honglin ; Libertini, Stephen J. ; George, Michael ; Dandekar, Satya ; Tepper, Clifford G. ; Al-Bataina, Bushra ; Kung, Hsing Jien ; Ghosh, Paramita M. ; Mudryj, Maria. / Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. In: Endocrine-Related Cancer. 2010 ; Vol. 17, No. 4. pp. 857-873.
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