RESUMEN

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.

Asunto(s)

Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Proteína Smad2/metabolismo , Proteína Smad4/metabolismo , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Estudios de Casos y Controles , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Masculino , Probabilidad , Hiperplasia Prostática/genética , Neoplasias de la Próstata/genética , Valores de Referencia , Muestreo , Sensibilidad y Especificidad , Proteína Smad2/genética , Proteína Smad4/genética , Técnicas de Cultivo de Tejidos , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo