title: Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers.
abstract: BACKGROUND
  Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer.
  
  
  METHODS
  Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression.
  
  
  RESULTS
  SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034).
  
  
  CONCLUSIONS
  SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance.
authors.affiliation: The University of Chicago, Chicago, Illinois, USA. rszmulew@medicine.bsd.uchicago.edu
authors.forename: Russell Z
authors.initials: RZ
authors.lastname: Szmulewitz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chung
authors.forename: Hikmat
authors.initials: H
authors.lastname: Al-Ahmadie
authors.forename: Silver
authors.initials: S
authors.lastname: Daniel
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: Aria
authors.initials: A
authors.lastname: Razmaria
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Zagaja
authors.forename: Charles B
authors.initials: CB
authors.lastname: Brendler
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Conzen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D000099184:Serum-Glucocorticoid Regulated Kinases; C410798:AR protein, human