Expression of TrkA, TrkB and TrkC in human neuroblastomas
Expression of TrkA, TrkB and TrkC in human neuroblastomas
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DOI：
10.1023/a:1005729329526
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发表时间：
1997-01-01
影响因子：
3.9
通讯作者：
Evans, AE
中科院分区：
文献类型：
--
作者：
Brodeur, GM;Nakagawara, A;Evans, AE
TRK家族的神经营养因子受体在调节正常和肿瘤神经细胞的存活、生长和分化中的作用引起了相当大的兴趣。事实上，越来越多的证据表明TRK基因在神经母细胞瘤（外周神经系统肿瘤）的生物学和临床行为中发挥重要作用。来自几项独立研究的证据表明，TrkA的高表达是有利结果的指标，并且TrkA表达与N-myc扩增之间存在负相关。此外，一些原发性神经母细胞瘤在体外存在NGF的情况下分化，但在缺乏NGF的情况下死亡。我们有证据表明，全长TrkB和BDNF的共表达与N-myc扩增相关，并可能代表自分泌生存途径。相反，截短的TrkB主要在分化的肿瘤中表达。最后，TrkC在有利的神经母细胞瘤中表达，基本上所有这些神经母细胞瘤也表达TrkA。总之，神经营养因子受体在神经母细胞瘤中的表达和功能的研究可能会提供重要的见解，这些途径在这种肿瘤的发病机制和临床行为中发挥的作用。最终，这些途径可能为开发旨在诱导这些肿瘤分化或程序性细胞死亡的治疗提供有吸引力的靶点。
There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors of the peripheral nervous system. Evidence from several independent studies suggests that high expression of TrkA is an indicator of favorable outcome, and there is an inverse correlation between TrkA expression and N-myc amplification. In addition, some primary neuroblastomas differentiate in vitro in the presence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification and may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, TrkC is expressed in favorable neuroblastomas, essentially all of which also express TrkA. In summary, the study of neurotrophin receptor expression and function in neuroblastomas may provide important insights into the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attractive targets for the development of therapy aimed at inducing differentiation or programmed cell death in these tumors.