Reversal of the low-affinity neurotrophin receptor stromal-epithelial expression pattern between benign and malignant human prostate

Abstract

Reduced expression of the low-affinity p75 neurotrophin receptor (p75 NTR) occurs in prostate epithelial cells during malignant transformation. Recent studies indicating that the p75 NTR can transduce signals that induce apoptosis suggest that diminished p75 NTR in transformed prostate cells may contribute to immortalization. Mutations in the transmembrane domain of the p75 NTR gene have been associated with decreased p75 NTR protein expression and may block the ability of the p75 NTR to induce apoptosis. Therefore, we used Western blot to analyze prostate cancer (PC) cell lines for p75 NTR protein expression and gene single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing to analyze mutations in the transmembrane domain of the p75 NTR. p75 NTR Protein was present in all cell lines, and mutations in the p75 NTR gene were not detected in cDNA derived from any cell line. To define the expression pattern of p75 NTR in PCs in vivo, we used immunohistochemical techniques to examine tissue specimens from 20 benign, 19 malignant primary, and 14 metastatic prostate specimens. In benign prostate tissues, expression of p75 NTR was universally detected in basal cells but not in secretory epithelial or stromal cells. In both primary and metastatic PC tissues, p75 NTR immunoreactivity could not be detected in malignant prostate epithelial cells. However, in contrast to the benign prostate, p75 NTR protein was expressed in stromal cells surrounding malignant epithelial cells. Stromal p75 NTR expression was present in 84% (16 of 19) primary and in 86% (12 of 14) metastatic specimens. These data show that in the benign prostate p75 NTR protein is expressed by basal cells and not stromal cells whereas in malignant prostate p75 NTR protein is expressed by stromal cells but not prostatic carcinoma cells. Reversal of the p75 NTR stromal-epithelial pattern of expression between benign and malignant prostate suggests that p75 NTR may contribute to the development and maintenance of prostate cancer.