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Departments of Anatomy and Cell Biology [B. R. P., M. O., D. D.] and Surgery, Division of Urology [J. H. L., D. D.], and The Lombardi Cancer Research Center [J. H. L., D. D.], Georgetown University Medical Center, Washington, D.C. 20007
In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an Mr 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.
1 This research was supported by a grant from the NIH (CA50229) to D.D.
2 To whom requests for reprints should be addressed, at Department of Anatomy and Cell Biology, Georgetown University School of Medicine, 3900 Reservoir Road, N.W., Washington, DC 20007.
Received 7/ 7/92. Accepted 8/18/92.
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