Localization of transforming growth factor-beta1 and type II receptor in developing normal human prostate and carcinoma tissues.

Abstract

Transforming growth factor-beta1 (TGF-beta1) is implicated in prostate development, and elevated expression of TGF-beta1 has been correlated with prostate carcinogenesis. In this study, cell type specificity of TGF-beta1 and TGF-beta receptor Type II (RcII) protein expression was determined by immunocytochemistry in human normal prostate and compared to prostate carcinoma tissues. Heterogeneous localization patterns of LAP-TGF-beta1 (TGF-beta1 precursor) and RcII were observed in both epithelial and mesenchymal cells in fetal prostate, with LAP-TGF-beta1 localizing to more basal epithelial cells. Homogeneity of LAP-TGF-beta1 staining was increased in neonatal, prepubertal, and adult prostate, with elevated immunoreactivity noted in epithelial acini relative to stromal tissue for both LAP-TGF-beta1 and RcII proteins. In stromal tissues, RcII cell localization exhibited staining patterns nearly identical to smooth muscle alpha-actin. In prostate carcinoma, LAP-TGF-beta1 localized to carcinoma cells with an increased staining heterogeneity relative to normal prostate. In contrast to normal epithelial cells, carcinoma epithelial cells exhibited low to nondetectable RcII staining. Stromal cell staining patterns for LAP-TGF-beta1 and RcII in carcinoma, however, were identical to those of normal prostate stromal cells. These studies implicate both epithelial and stromal cells as sites of TGF-beta1 synthesis and RcII localization in the developing and adult normal human prostate. In addition, these data indicate a loss of epithelial expression of RcII concurrent with altered LAP-TGF-beta1 expression in human prostate carcinoma cells.