title: Inhibition of aberrant androgen receptor induction of prostate specific antigen gene expression, cell proliferation and tumor growth by 17α-estradiol in prostate cancer.
abstract: OBJECTIVE
  Androgen independent prostate cancer growth and metastasis are a major cause of prostate cancer death. Aberrant androgen receptor activation due to androgen receptor mutation is an important mechanism of androgen independence. We determined the effectiveness and mechanism of 17α-estradiol (Sigma®) in blocking aberrant androgen receptor activation due to androgen receptor mutation.
  
  
  METHODS
  We used LNCaP and MDA Pca-2b prostatic tumor cells (ATCC®) containing a mutated androgen receptor and WT estrogen receptor β to test 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression and cell growth. Cotransfection analysis was used to further elucidate the mechanism of 17α-estradiol action. Xenograft animals with an LNCaP prostate tumor were prepared to study the in vivo effect of 17α-estradiol on tumor growth inhibition.
  
  
  RESULTS
  In LNCaP cells 17α-estradiol produced a dose dependent inhibition of cyproterone acetate (Sigma) or dihydrotestosterone induced prostate specific antigen gene expression. In MDA Pca-2b cells 17α-estradiol inhibited cortisol (Sigma) induced prostate specific antigen expression and blocked dihydrotestosterone and cortisol induced cell proliferation in LNCaP and MDA Pca-2b cells, respectively. Cotransfection analysis showed that 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression was medicated via estrogen receptors. In xenograft mice with LNCaP prostate cancer 17α-estradiol but not 17β-estradiol (Sigma) significantly inhibited tumor growth, although each estrogen tended to decrease tumor growth.
  
  
  CONCLUSIONS
  Results suggest that 17α-estradiol with less classic estrogenic activity is a potential therapeutic agent for androgen independent prostate cancer due to androgen receptor mutation.
authors.affiliation: Department of Medicine/Endocrinology, Weill Medical College of Cornell University, New York, New York 10065, USA. yuz2002@med.cornell.edu
authors.forename: Yaming
authors.initials: Y
authors.lastname: Qiao
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Cai
authors.forename: Chen
authors.initials: C
authors.lastname: Tan
authors.forename: Julianne
authors.initials: J
authors.lastname: Imperato-McGinley
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
mesh_terms: D059002:Androgen Receptor Antagonists; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D059002:Androgen Receptor Antagonists; D004967:Estrogens; D004958:Estradiol; D017430:Prostate-Specific Antigen