Sortino M A, Condorelli F, Vancheri C, Chiarenza A, Bernardini R, Consoli U, Canonico P L
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Mol Endocrinol. 2000 Jan;14(1):124-36. doi: 10.1210/mend.14.1.0402.
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, p140trka. Only p140trka, but not the low-affinity NGF receptor, p75LNGFR, was expressed in LNCaP cells; both the proliferative response and the phosphorylation of p140trka upon NGF treatment were prevented by the tyrosine kinase inhibitor K252a. LNCaP cells transiently transfected with the cDNA encoding for p75LNGFR appeared more sensitive to NGF, as demonstrated by the increased number of p75LNGFR-transfected LNCaP cells exposed for 72 h to NGF compared with wild LNCaP cultures. However, p75LNGFR-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.
我们研究了神经生长因子（NGF）对雄激素依赖的前列腺腺癌LNCaP细胞系的作用。将LNCaP细胞暴露于NGF会导致细胞增殖显著增加。该作用呈浓度依赖性，在补充血清或活性炭处理的血清以及血清剥夺条件下均同样存在。NGF的促有丝分裂作用伴随着前列腺特异性抗原（PSA）表达的增强，并且与二氢睾酮的增殖作用相加。NGF的增殖作用似乎是由高亲和力NGF受体p140trka介导的。LNCaP细胞中仅表达p140trka，而不表达低亲和力NGF受体p75LNGFR；酪氨酸激酶抑制剂K252a可阻止NGF处理后p140trka的增殖反应和磷酸化。与野生LNCaP培养物相比，用编码p75LNGFR的cDNA瞬时转染的LNCaP细胞对NGF似乎更敏感，这表现为暴露于NGF 72小时后，p
