title: Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic hyperplasia after androgen deprivation.
abstract: OBJECTIVE
  Benign prostatic hyperplasia (BPH) is related to advancing age and the presence of androgens and occurs in virtually all older men. BPH causes morbidity, most often by urinary obstruction, in a substantial fraction of men over sixty. Both finasteride and androgen ablation induce partial diminution in BPH that occurs over weeks to months. This is in contrast to the often rapid involution seen in both normal prostatic epithelium and prostatic carcinoma in response to androgen withdrawal. This study was performed to analyze the response of prostatic cells, and in particular BPH, to acute androgen ablation.
  
  
  METHODS
  We subjected a cohort of 26 men to androgen ablation with goserelin, a gonadotrophin releasing hormone agonist, for 3-4 weeks prior to radical prostatectomy for prostate cancer. Preablation biopsy specimens and prostatectomy specimens were immunohistochemically stained for apoptotic cells and for expression of apoptosis regulatory proteins Bcl-2, Bax, Bcl-x, and Bak.
  
  
  RESULTS
  Normal prostatic epithelial cells and prostate cancer responded to hormone deprivation by undergoing apoptosis, but in 19/26 specimens prostatic hyperplasia had a total absence of apoptosis. In all 26 specimens, benign prostatic hyperplasia demonstrated increased expression of the Bcl-2 protein, but no change in the expression of Bax, Bcl-x, and Bak. In contrast, adjacent normal and malignant prostatic epithelium showed positive staining for apoptosis and did not alter Bcl-2 expression in response to androgen ablation.
  
  
  CONCLUSIONS
  BPH demonstrated increased staining for Bcl-2 after androgen deprivation that may render hyperplastic epithelium relatively resistant to apoptosis induced acutely by androgen withdrawal.
authors.affiliation: Department of Medicine, Lombardi Cancer Center, Georgetown University School of Medicine, Washington DC 20007, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cardillo
authors.forename: G
authors.initials: G
authors.lastname: Berchem
authors.forename: M A
authors.initials: MA
authors.lastname: Tarkington
authors.forename: S
authors.initials: S
authors.lastname: Krajewski
authors.forename: M
authors.initials: M
authors.lastname: Krajewski
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: T
authors.initials: T
authors.lastname: Tehan
authors.forename: L
authors.initials: L
authors.lastname: Ortega
authors.forename: J
authors.initials: J
authors.lastname: Lage
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone