Mitogenic effect of nerve growth factor (NGF) in LNCaP prostate adenocarcinoma cells: Role of the high- and low-affinity NGF receptors

We have investigated the effect of nerve growth factor (NGF) in the androge n-dependent, prostate adenocarcinoma LNCaP cell line. Exposure of LNCaP cel ls to NGF resulted in a significant increase of cell proliferation. The eff ect was concentration dependent and equally present in serum- or charcoal-s tripped serum-supplemented and serum-deprived conditions. The mitogenic act ion of NGF was accompanied by an enhanced expression of prostate-specific a ntigen (PSA) and resulted additive to the proliferative effect of dihydrote stosterone. The proliferative effect of NGF appeared to be mediated by the high-affinity NGF receptor, p140(trka). Only p140(trka), but not the low-af finity NGF receptor, p75(LNGFR), was expressed in LNCaP cells; both the pro liferative response and the phosphorylation of p140(trka) upon NGF treatmen t were prevented by the tyrosine kinase inhibitor K252a. LNCaP cells transi ently transfected with the cDNA encoding for p75(LNGFR) appeared more sensi tive to NGF, as demonstrated by the increased number of p75(LNGFR)-transfec ted LNCaP cells exposed for 72 h to NGF compared with wild LNCaP cultures. However, p75(LNGFR)-transfected LNCaP cells rapidly underwent apoptotic dea th when deprived of NGF. Our study demonstrates the physiological relevance of NGF in the regulation of prostate cell proliferation and the relative c ontribution of the high- end low-affinity NGF receptors in this control.