Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression

Prostate. 2004 May 15;59(3):234-42. doi: 10.1002/pros.10361.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / biosynthesis*
  • Cell Transformation, Neoplastic*
  • Cohort Studies
  • DNA-Binding Proteins / biosynthesis*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Prostatectomy
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Signal Transduction
  • Smad4 Protein
  • Smad8 Protein
  • Trans-Activators / biosynthesis*
  • Transforming Growth Factor beta


  • BMP2 protein, human
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • SMAD4 protein, human
  • SMAD9 protein, human
  • Smad4 Protein
  • Smad4 protein, rat
  • Smad8 Protein
  • Trans-Activators
  • Transforming Growth Factor beta