Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression.
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.
Horvath
Lisa G
LG
Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
Henshall
Susan M
SM
Kench
James G
JG
Turner
Jennifer J
JJ
Golovsky
David
D
Brenner
Phillip C
PC
O'Neill
Gordon F
GF
Kooner
Raji
R
Stricker
Phillip D
PD
Grygiel
John J
JJ
Sutherland
Robert L
RL
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
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