Role of the low‐affinity nerve growth factor receptor and the high‐affinity trk nerve growth factor receptor in human prostate carcinogenesis

Daniel Djakiew, Robert Delsite, Rakhi Dalai, Beth Pflug

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Nerve growth factor (NGF) interacts with a low‐affinity NGF receptor (LNGFR) and a high‐affinity Trk receptor in the paracrine regulation of human prostate growth. Both the LNGFR and the Trk receptor localize to the epithelia of the normal prostate. During malignant progression of the prostate, expression of the LNGFR is progressively lost from the epithelia, whereas Trk expression is retained in the epithelia of the adenomatous foci. Human prostatic stromal cell secretory protein (hPS) containing NGF stimulates autophosphorylation of the Trk receptor in a time‐ and concentration‐dependent manner. This effect appears to be broadly based, because three distinct human prostate tumor cell lines (TSU‐pr1, DU‐145, and PC‐3) were shown to undergo Trk autophosphorylation in response to treatment with hPS. These observations are of potential significance, because the LNGFR is thought to participate in the inhibition of prostate growth via apoptotic mechanisms, whereas the Trk receptor is thought to participate in the stimulation of prostate growth via initiation of a phosphorylation cascade. Therefore, loss of the LNGFR may eliminate an inhibitor of prostate growth as well as reducing competition for the NGF ligand, thereby enhancing a growth stimulus to the prostate tissues mediated via the Trk receptor. In this manner, an alteration in the balance of growth regulation between the inhibitory effect of the LNGFR and the stimulatory effect of the Trk receptor may play a causal role in prostate carcinogenesis. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalRadiation Oncology Investigations
Volume3
Issue number6
DOIs
StatePublished - 1995

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Keywords

  • LNGFR
  • NGF
  • Trk
  • paracrine
  • prostate

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging

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