Expression of a Trk high affinity nerve growth factor receptor in the human prostate

Beth Pflug, C. Dionne, D. R. Kaplan, J. Lynch, D. Djakiew

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Nerve growth factor-β (NGFβ) and a NGFβ-immunoreactive protein derived from human prostatic stromal cell secretory protein (hPS) have been shown to stimulate the growth of prostate epithelial cells. An NGFβ-immunoreactive protein has been localized to the stroma of human prostate tissues, and a low affinity NGF receptor (gp75(NGFR)) has been localized to the adjacent epithelia, consistent with the paracrine regulation of prostate growth. Interestingly, gp75(NGFR) is progressively lost during neoplastic progression of the human prostate. In this report we have characterized the expression of the signal-transducing component of the NGF receptor, the Trk tyrosine receptor kinase, in prostate epithelial cells that bind exogenous NGFβ and an endogenous NGFβ-immunoreactive protein in hPS. In this context, a pan- Trk antibody that recognizes all of the members of the Trk receptor family (TrkA, TrkB, and TrkC) specifically localized expression of the Trk receptor to the epithelial component of normal prostate tissue, benign prostatic hyperplasia, and adenocarcinoma tissue. The binding of [125I]NGFβ to the surface of primary cultures of human prostate epithelia and the TSU-pr1 human metastatic prostate tumor cell line was displaced with either excess cold NGFβ or hPS, whereas binding was not displaced by epidermal growth factor or platelet-derived growth factor. Scatchard plot analysis of [125I]NGFβ binding to these cells identified a low affinity binding site (K(d) = 1.9 x 10-9 M) and a high affinity binding site (K(d) = 1.8 x 10-11 M) on the primary prostate epithelia, whereas only a high affinity binding site (K(d) = 1.3 x 10-11 M) was observed on the TSU-pr1 tumor cells. Stimulation of TSU-pr1 cells with either NGFβ or hPS induced tyrosine phosphorylation of Trk proteins, whereas no phosphorylation was evident in untreated cells, cells treated with hPS immunoprecipitated with anti-NGFβ antibody, or brain- derived neurotrophic factor- and neurotrophin-3-treated cells. The Trk protein was also observed in these cells by immunoblot analysis with pan-Trk antibody. These results demonstrate a functional Trk receptor in the epithelia of the human prostate that is responsive to exogenous NGFβ and an endogenous NGFβ-immunoreactive protein in hPS, thereby supporting the concept of the paracrine regulation of growth in the human prostate via a stromal neurotrophin-epithelial Trk receptor interaction.

Original languageEnglish (US)
Pages (from-to)262-268
Number of pages7
JournalEndocrinology
Volume136
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Nerve Growth Factor Receptor
Nerve Growth Factor
Prostate
Epithelium
Proteins
Binding Sites
Antibodies
Growth
trkA Receptor
Epithelial Cells
Phosphorylation
Neurotrophin 3
Platelet-Derived Growth Factor
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Prostatic Hyperplasia
Receptor Protein-Tyrosine Kinases
Stromal Cells
Tumor Cell Line
Epidermal Growth Factor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Pflug, B., Dionne, C., Kaplan, D. R., Lynch, J., & Djakiew, D. (1995). Expression of a Trk high affinity nerve growth factor receptor in the human prostate. Endocrinology, 136(1), 262-268.

Expression of a Trk high affinity nerve growth factor receptor in the human prostate. / Pflug, Beth; Dionne, C.; Kaplan, D. R.; Lynch, J.; Djakiew, D.

In: Endocrinology, Vol. 136, No. 1, 1995, p. 262-268.

Research output: Contribution to journalArticle

Pflug, B, Dionne, C, Kaplan, DR, Lynch, J & Djakiew, D 1995, 'Expression of a Trk high affinity nerve growth factor receptor in the human prostate', Endocrinology, vol. 136, no. 1, pp. 262-268.
Pflug, Beth ; Dionne, C. ; Kaplan, D. R. ; Lynch, J. ; Djakiew, D. / Expression of a Trk high affinity nerve growth factor receptor in the human prostate. In: Endocrinology. 1995 ; Vol. 136, No. 1. pp. 262-268.
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