title: High SPDEF may identify patients who will have a prolonged response to androgen deprivation therapy.
abstract: BACKGROUND
  Due to the indolent nature of prostate cancer, new prognostic measures are needed to identify patients with life threatening disease. SAM pointed domain-containing Ets transcription factor (SPDEF) has been associated with good prognosis and demonstrates an intimate relationship with the androgen receptor (AR), however its role in prostate cancer progression remains unclear.
  
  
  METHODS
  A tissue microarray constructed from cores of 713 consecutive radical prostatectomy specimens were immunohistochemically stained for SPDEF and correlated with progression free and metastatic free survival. In vitro studies assessed growth rate, migration, and sensitivity to bicalutamide to explore mechanisms behind the tissue microarray observations.
  
  
  RESULTS
  Patients with high SPDEF demonstrate longer metastases free survival after receiving the standard of care (HR = 9.80, P = 0.006). SPDEF expression corresponded with bicalutamide growth inhibition and apoptosis induction in all cell lines studied. In addition, a feedforward loop of AR-SPEF expression regulation is observed.
  
  
  CONCLUSIONS
  SPDEF may be clinically useful to identify patients who will have extended benefits from androgen deprivation therapy. In vitro observations suggest SPDEF mediates initial sensitivity to androgen deprivation therapy through both AR regulation and downstream events.
authors.affiliation: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, 14263.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Haller
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Rochelle
authors.initials: R
authors.lastname: Payne-Ondracek
authors.forename: Willie
authors.initials: W
authors.lastname: Underwood
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D009570:Nitriles / Q000627:therapeutic use*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D014105:Tosyl Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D050783:Proto-Oncogene Proteins c-ets; D011944:Receptors, Androgen; C403974:SPDEF protein, human; D014105:Tosyl Compounds; C053541:bicalutamide
keywords: SPDEF; androgen receptor; metastasis; prostate