title: Expression profiles and functional associations of endogenous androgen receptor and caveolin-1 in prostate cancer cell lines.
abstract: BACKGROUND
  In prostate cancer (PCa) patients, the protein target for androgen deprivation and blockade therapies is androgen receptor (AR). AR interacts with many proteins that function to either co-activate or co-repress its activity. Caveolin-1 (Cav-1) is not found in normal prostatic epithelium, but is found in PCa, and may be an AR co-regulator protein.
  
  
  METHODS
  We investigated cell line-specific signatures and associations of endogenous AR and Cav-1 in six PCa cell lines of known androgen sensitivity: LNCaP (androgen sensitive); 22Rv1 (androgen responsive); PC3, DU145, and ALVA41 (androgen non-reliant); and RWPE1 (non-malignant). Protein and mRNA expression profiles were compared and electron microscopy used to identify cells with caveolar structures. For cell lines expressing both AR and Cav-1, knockdown techniques using small interfering RNA against AR or Cav-1 were used to test whether diminished expression of one affected the other. Co-sedimentation of AR and Cav-1 was used to test their association. A reporter assay for AR genomic activity was utilized following Cav-1 knockdown.
  
  
  RESULTS
  AR-expressing LNCaP and 22Rv1 cells had low endogenous Cav-1 mRNA and protein. Cell lines that expressed little or no AR (DU145, PC3, ALVA41, and RWPE1) expressed high endogenous levels of Cav-1. AR knockdown in LNCaP cells had little effect on Cav-1, but Cav-1 knockdown inhibited AR expression and genomic activity.
  
  
  CONCLUSIONS
  These data show endogenous AR and Cav-1 mRNA and protein expression is inversely related in PCa cells, with Cav-1 acting on the androgen/AR signaling axis possibly as an AR co-activator, demonstrated by diminished AR genomic activity following Cav-1 knockdown.
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, Australia.
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Bennett
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
mesh_terms: D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051242:Caveolin 1; D034741:RNA, Small Interfering; D011944:Receptors, Androgen
keywords: androgen deprivation; androgen-dependent; androgen-sensitive; co-activator; prostate; prostate cancer