Papatsoris Athanasios G, Liolitsa Danae, Deliveliotis Charalambos
2nd Department of Urology, University of Athens, School of Medicine, Sismanoglio General Hospital, Athens, Greece.
Expert Opin Investig Drugs. 2007 Mar;16(3):303-9. doi: 10.1517/13543784.16.3.303.
Autocrine and paracrine events regulated by nerve growth factor (NGF) and relevant receptors (low- and high affinity; p75 neurotrophin receptor [p75(NTR)] and TrkA, respectively) seem to play a significant role in prostate carcinogenesis. Studies reveal that p75(NTR) is both a tumor suppressor of growth and a metastasis suppressor of human prostate cancer cells. Furthermore, p75(NTR) is progressively lost during prostate carcinogenesis. An imbalance between p75(NTR) and tropomyosin receptor kinase A (TrkA)-mediated signals may be involved in the progression of prostate cancer through increased proliferation and reduced apoptosis. The antiproliferative and apoptotic effects of GnRH analogs in prostate cancer cells may be mediated by altering the TrkA:p75(NTR) NGF receptor ratio. Administration of NGF induces a reversion of the androgen-independent/androgen receptor-negative prostate cancer cell lines to a less malignant phenotype. Finally, Trk inhibition is a novel, attractive and rational approach for prostate cancer therapy. This review unravels the NGF 'circuitry' in prostate cancinogenesis for relevant pharmacologic manipulation to lead to the development of novel therapeutic agents.
由神经生长因子（NGF）和相关受体（分别为低亲和力和高亲和力；p75神经营养因子受体[p75(NTR)]和TrkA）调节的自分泌和旁分泌事件似乎在前列腺癌发生过程中起重要作用。研究表明，p75(NTR)既是生长的肿瘤抑制因子，也是人前列腺癌细胞的转移抑制因子。此外，在前列腺癌发生过程中p75(NTR)会逐渐丧失。p75(NTR)和原肌球蛋白受体激酶A（TrkA）介导的信号之间的失衡可能通过增加增殖和减少凋亡参与前列腺癌的进展。GnRH类似物在前列腺癌细胞中的抗增殖和凋亡作用可能是通过改变TrkA:p75(NTR) NGF受体比例来介导的。给予NGF可诱导雄激素非依赖性/雄激素受体阴性前列腺癌细胞系转变为恶性程度较低的表型。最后，抑制Trk是一种新颖、有吸引力且合理的前列腺癌治疗方法。本综述揭示了前列腺癌发生过程中的NGF“信号通路”，以便进行相关的药理操作，从而开发新型治疗药物。
