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Mitogenic Effect of Nerve Growth Factor (NGF) in LNCaP Prostate Adenocarcinoma Cells: Role of the High- and Low-Affinity NGF Receptors

Institutes of Pharmacology (M.A.S., F.C., A.C., R.B.), Respiratory Diseases (C.V.), and Hematology (U.C.) University of Catania School of Medicine 95125 Catania, Italy
Department of Internal Medicine (P.L.C.) Section of Pharmacology University of Pavia School of Medicine 27100 Pavia, Italy

We have investigated the effect of nerve growth factor (NGF) in the androgen-dependent, prostate adenocarcinoma LNCaP cell line. Exposure of LNCaP cells to NGF resulted in a significant increase of cell proliferation. The effect was concentration dependent and equally present in serum- or charcoal-stripped serum-supplemented and serum-deprived conditions. The mitogenic action of NGF was accompanied by an enhanced expression of prostate-specific antigen (PSA) and resulted additive to the proliferative effect of dihydrotestosterone. The proliferative effect of NGF appeared to be mediated by the high-affinity NGF receptor, p140^trka. Only p140^trka, but not the low-affinity NGF receptor, p75^LNGFR, was expressed in LNCaP cells; both the proliferative response and the phosphorylation of p140^trka upon NGF treatment were prevented by the tyrosine kinase inhibitor K252a. LNCaP cells transiently transfected with the cDNA encoding for p75^LNGFR appeared more sensitive to NGF, as demonstrated by the increased number of p75^LNGFR-transfected LNCaP cells exposed for 72 h to NGF compared with wild LNCaP cultures. However, p75^LNGFR-transfected LNCaP cells rapidly underwent apoptotic death when deprived of NGF. Our study demonstrates the physiological relevance of NGF in the regulation of prostate cell proliferation and the relative contribution of the high- and low-affinity NGF receptors in this control.

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