DOWN-REGULATION OF PROTEIN AND MESSENGER-RNA EXPRESSION FOR TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA-1) TYPE-I AND TYPE-II RECEPTORS IN HUMAN PROSTATE-CANCER

Transforming growth factor-beta (TGF-beta I) is a potent negative regu lator of cell growth that transduces signals through interactions with type I and II receptors. Abnormal expression and mutational alteratio ns of these receptors have been observed in several human malignancies . In this study, we investigated the expression of the two types of TG F-beta I receptors, R-I and R-II, in a normal human prostate, primary prostate adenocarcinoma and lymph nodes with metastatic deposits, Expr ession of receptor proteins was examined by immunohistochemical analys is in paraffin-embedded prostatic tissue sections, and mRNA expression was determined by Northern blot and RT-PCR analysis, Uniformly strong immunoreactivity for both TGF-beta receptor proteins, R-I and R-II, w as exclusively localized to the prostatic glandular epithelium of norm al prostates, In contrast, tumor epithelial cells in primary and metas tatic prostatic cancer specimens exhibited a weak heterogeneous immuno reactivity for both R-I and R-II receptors; 25% of primary prostatic t umors and 45% of the lymph nodes with metastases were totally negative for R-I and R-II expression, while the rest exhibited a significantly reduced immunoreactivity for both types of receptors compared to the normal prostate (p < 0.05), Moreover, there was a significant decrease in the expression of R-I and R-II mRNA, in all 20 primary prostatic t umors and 4 lymph nodes positive for metastases, indicating that the d ecreased protein expression was due to down-regulation of gene express ion for the two receptors, Our findings imply that decreased expressio n of TGF-beta I type I and type II receptors might be involved in pros tate tumorigenesis. (C) 1997 Wiley-Liss, Inc.