Mitogenic effect of nerve growth factor (NGF) in LNCaP prostate adenocarcinoma cells: Role of the high- and low-affinity NGF receptors
Mitogenic effect of nerve growth factor (NGF) in LNCaP prostate adenocarcinoma cells: Role of the high- and low-affinity NGF receptors
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DOI：
10.1210/me.14.1.124
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发表时间：
2000-01-01
影响因子：
--
通讯作者：
Canonico, PL
中科院分区：
文献类型：
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作者：
Sortino, MA;Condorelli, F;Canonico, PL
我们研究了神经生长因子(NGF)在雄激素依赖性前列腺癌LNCaP细胞系中的作用。LNCaP细胞暴露于NGF后，细胞增殖明显增强。这种影响是浓度依赖的，在补充血清或去除木炭的血清补充和去除血清的条件下，这种影响同样存在。NGF的促有丝分裂作用伴随着前列腺特异性抗原(PSA)的表达增强，并与双氢睾酮的增殖作用相辅相成。NGF的增殖作用可能是通过高亲和力的NGF受体p140(TrkA)介导的。在LNCaP细胞中只表达p140(TrkA)，而不表达低亲和力的NGF受体p75(LNGFR)；酪氨酸激酶抑制剂K252a可阻止NGF处理后的增殖反应和p140(TrkA)的磷酸化。瞬时转导p75(LNGFR)基因的LNCaP细胞对NGF更为敏感，与野生型LNCaP细胞相比，转导p75(LNGFR)基因的LNCaP细胞72 h后对NGF的敏感性增加。然而，p75(LNGFR)转基因的LNCaP细胞在缺乏NGF的情况下迅速发生凋亡死亡。我们的研究证明了NGF在调节前列腺细胞增殖中的生理学相关性，以及高端低亲和力NGF受体在这一对照中的相对贡献。
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- end low-affinity NGF receptors in this control.