The low-affinity nerve growth factor receptor p75NTR is a 75-kDa glycoprotein that belongs to the tumor necrosis factor receptor superfamily and has been implicated in the induction of apoptosis in various tissues and cell lines. Immunohistochemistry on tissue sections from radical prostatectomies has shown that expression of p75NTR is limited to the epithelial cells. Western blot and immunohistochemical analyses have also shown a progressive loss of p75NTR expression in prostate epithelial cells during the malignant progression of organ-confined adenocarcinomas, with complete loss of expression in the naturally occurring prostate tumor cell lines DU-145, PC-3, LNCaP, and TSU-pr1, which were derived from metastases. Reintroduction of p75NTR expression into the TSU-pr1 tumor cell line was shown to reestablish the ability of these cells to undergo p75NTR-mediated apoptosis. It is not known whether this loss of expression is due to deletion of part or the entire p75NTR gene or to other factors. Through the use of southern blotting and polymerase chain reaction (PCR), we showed that loss of p75NTR protein expression was not due to deletion or loss of the gene. Furthermore, through reverse transcription–PCR, RNase protection, and the chromatin immunoprecipitation assay, we showed that transcription of the p75NTR gene occurred in these prostate tumor cell lines. Finally, through transient transfection using two constructs of p75NTR, one containing the full 2-kb 3′ untranslated region and one that contains only a few hundred bases of the 3′ untranslated region (UTR), we showed that the 3′ UTR may have a role in the loss of p75NTR expression in prostate cancer. © 2001 Wiley-Liss, Inc.