title: Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression.
abstract: BACKGROUND
  The role of the bone morphogenetic protein (BMP) pathway in prostate cancer (PC) is unclear. This study aimed to characterize aspects of the BMP pathway in PC by assessing BMP2, Smad8, and Smad4 expression in normal, hyperplastic, and malignant prostate tissue, and to correlate findings with progression to PC.
  
  
  METHODS
  Radical prostatectomy (RP) specimens from 74 patients with clinically localized PC (median follow-up 51 months, range 15-152), 44 benign prostatic hypertrophy (BPH) lesions, and 4 normal prostates (NPs) were assessed for BMP2, Smad8, and Smad4 expression using immunohistochemistry.
  
  
  RESULTS
  Both BMP2 (P < 0.001) and nuclear Smad4 (P < 0.0001) expression were significantly decreased in PC compared to benign prostate tissue. Nuclear Smad8 was present in normal/benign prostate tissue but absent in PC and adjacent hyperplasia. Furthermore, loss of BMP2 (P < 0.001) and decreased nuclear Smad4 (P = 0.05) expression correlated with increasing Gleason score.
  
  
  CONCLUSIONS
  These data suggest that decreased BMP2, nuclear smad8 and nuclear Smad4 expression are associated with the progression to PC, and in particular loss of BMP2 and Smad4 are related to progression to a more aggressive phenotype.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
authors.forename: Susan M
authors.initials: SM
authors.lastname: Henshall
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Turner
authors.forename: David
authors.initials: D
authors.lastname: Golovsky
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Brenner
authors.forename: Gordon F
authors.initials: GF
authors.lastname: O'Neill
authors.forename: Raji
authors.initials: R
authors.lastname: Kooner
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stricker
authors.forename: John J
authors.initials: JJ
authors.lastname: Grygiel
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D000328:Adult; D000368:Aged; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D015398:Signal Transduction; D051901:Smad4 Protein; D051904:Smad8 Protein; D015534:Trans-Activators / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; C107514:SMAD9 protein, human; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D051904:Smad8 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta