title: Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells.
abstract: BACKGROUND
  Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear.
  
  
  METHODS
  We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined.
  
  
  RESULTS
  PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone.
  
  
  CONCLUSIONS
  PTEN induction confers androgen independent CaP cells enhanced responsiveness to the anti-proliferative effects of anti-androgens and this action may involve non-AR mediated effects.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Conaway
authors.forename: D
authors.initials: D
authors.lastname: Gioeli
authors.forename: M J
authors.initials: MJ
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Theodorescu
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000235:genetics* / Q000503:physiopathology*; D009570:Nitriles; D051058:Oncogene Protein v-akt / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000502:physiology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014105:Tosyl Compounds; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D016159:Tumor Suppressor Protein p53; C053541:bicalutamide; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017430:Prostate-Specific Antigen; D004318:Doxycycline