title: Divergent effect of liver X receptor agonists on prostate-specific antigen expression is dependent on androgen receptor in prostate carcinoma cells.
abstract: BACKGROUND
  Liver X receptor (LXR) isoforms, LXRα and LXRβ, have similar protein structures and ligands, but diverse tissue distribution. We used two synthetic, non-steroidal LXR agonists, T0901317 and GW3965, to investigate the effects of LXR agonist modulation on prostate specific antigen (PSA) via the expressions of androgen receptors (AR), LXRα, or LXRβ, in prostate carcinoma cells.
  
  
  METHODS
  LXRα- or LXRβ-knockdown cells were transduced with specific shRNA lentiviral particles. LXRα and LXRβ expressions were assessed by immunoblotting and RT-qPCR assays. Cell proliferation was determined by (3) H-thymidine incorporation assays. The effects of LXR agonists and epigallocatechin gallate (EGCG) on PSA expression were determined by ELISA, immunoblotting, or transient gene expression assays.
  
  
  RESULTS
  Treatment with either T0901317 or GW3965 significantly attenuated cell proliferation of LNCaP cells. T0901317 treatment suppressed PSA expression while GW3965 treatment enhanced PSA expression. The increase of PSA promoter activity by GW3965 was dependent on the expression of AR. Either LXRα- or LXRβ-knockdown did not affect the activation of androgen on PSA gene expression. However, as compared with mock knockdown-LNCaP cells, the LXRα-knockdown but not the LXRβ-knockdown attenuated the effects of T0901317 and GW3965 on PSA expressions. The effect of GW3965 on PSA expression was blocked by the addition of EGCG.
  
  
  CONCLUSIONS
  Our results indicate that T0901317 and GW3965 have divergent effects on PSA expressions. The effects of LXR agonists on PSA expression are LXRα-dependent and AR-dependent. EGCG blocks the inducing effect of GW3965 on PSA expression.
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital-Linko, Kwei-Shan, Tao-Yuan, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Tsui
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chung
authors.forename: Tsui-Hsia
authors.initials: TH
authors.lastname: Feng
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Lee
authors.forename: Phei-Lang
authors.initials: PL
authors.lastname: Chang
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Chen
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000032:analysis; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D001565:Benzoates; D001596:Benzylamines; D002392:Catechin; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D017430:Prostate-Specific Antigen; D011944:Receptors, Androgen; D013449:Sulfonamides; C410798:AR protein, human; C473027:GW 3965; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C045651:epigallocatechin gallate
keywords: EGCG; GW3965; LXR receptor; T0901317; androgen receptor; prostate specific antigen