Altered levels of Smad2 and Smad4 are associated with human prostate carcinogenesis.
Alterations have been demonstrated in ligand and cognate receptor system of the transforming growth factor beta (TGF-beta) pathway in prostate cancer (PC). Still, little is known about changes in the activity of the intracellular Smad cascade of TGF-beta signaling during prostate carcinogenesis. We used immunohistochemistry to analyze phosphorylated Smad2 (p-Smad2), nuclear Smad4 and inhibitory-Smad7 in epithelial cells of normal, hyperplastic and malignant prostate. Specimens comprised 49 tissue cores of PC, 10 benign prostate hypertrophies and three normal prostates. Nuclear p-Smad2 (P<0.001) and nuclear Smad4 (P=0.023) were significantly decreased in PC with remarkable variations in cytoplasmic Smad7 levels. Substantial decreases in p-Smad2 and Smad4 levels were found in specimens with primary Gleason grades 3 and 4, whereas in grade 5, levels were markedly higher. Our results provide the first evidence for changes and reversible attenuation in the Smad system of the TGF-beta pathway during prostate carcinogenesis.
Perttu
M C
MC
Department of Anatomy, Medical School, University of Tampere, Tampere, Finland. mika.perttu@uta.fi
Martikainen
P M
PM
Huhtala
H S A
HS
Bläuer
M
M
Tammela
T L J
TL
Tuohimaa
P J
PJ
Syvälä
H
H
D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D051899:Smad2 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta