title: Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis.
abstract: BACKGROUND
  Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells.
  
  
  METHODS
  We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs.
  
  
  RESULTS
  Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease.
  
  
  CONCLUSIONS
  Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Farideh
authors.initials: F
authors.lastname: Mehraein-Ghomi
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Church
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Hirak S
authors.initials: HS
authors.lastname: Basu
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D000728:Androgens; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000099228:Diamine N-Acetyltransferase
keywords: SSAT; biomarker for progression; cancer prognosis; oxidative Stress