title: Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells.
abstract: BACKGROUND
  Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model.
  
  
  METHODS
  Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR.
  
  
  RESULTS
  Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen.
  
  
  CONCLUSIONS
  ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.
authors: Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China. dryongwangfmmu@yahoo.com.cn
authors: Y
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authors: Wang
authors: J-Q
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authors: Li
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authors: Shao
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authors: Shi
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authors: Liu
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authors: Yang
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authors: Qiu
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authors: Li
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authors: Zhang
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authors: Xue
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authors: Lei
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authors: Yuan
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authors: Bao
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authors: YT
authors: Zhang
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005485:Flutamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics; D056918:Nuclear Receptor Coactivators / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000726:Androgen Antagonists; C498001:NCOA2 protein, human; C111382:NCOA4 protein, human; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D051958:Nuclear Receptor Coactivator 2; D056918:Nuclear Receptor Coactivators; D012333:RNA, Messenger; C014290:hydroxyflutamide; D005485:Flutamide