The norepinephrine transporter and pheochromocytoma
The norepinephrine transporter and pheochromocytoma
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DOI：
10.1196/annals.1353.029
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Phillips, Jacqueline K.
中科院分区：
文献类型：
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作者：
Cleary, Susannah;Phillips, Jacqueline K.
嗜铬细胞瘤是罕见的嗜铬细胞来源的神经内分泌肿瘤，其合成和分泌过量的儿茶酚胺和其他血管活性肽。嗜铬细胞瘤还表达去甲肾上腺素转运蛋白（NET），这种分子在临床上被用作将放射性标记的底物（如I-131-MIBG（碘-间甲基苄基胍））整合到嗜铬细胞瘤细胞中的手段。这使得这些肿瘤的诊断定位成为可能，最近，I-131-MIBG已被用于治疗嗜铬细胞瘤的试验中，可能会产生NET作为治疗靶点。然而，由于转运体的水平或活性不同，I-131-MIBG持续融入肿瘤细胞的能力受到限制，因此正在研究各种增加NET功能活性的策略，包括使用传统的化疗药物，如顺铂或阿霉素。在这篇简短的综述中讨论的NET的其他方面包括转运体的调节，以及NET与结构（如syntaxin 1A）之间的新型蛋白-蛋白相互作用如何成为提高I-131-MIBG治疗价值的创新方法的关键。
Pheochromocytomas are rare neuroendocrine tumors of chromaffin cell origin that synthesize and secrete excess quantities of catecholamines and other vasoactive peptides. Pheochromocytomas also express the norepinephrine transporter (NET), a molecule that is used clinically as a means of incorporating radiolabelled substrates such as I-131-MIBG (iodo-metaiodobenzylguanidine) into pheochromocytoma tumor cells. This allows the diagnostic localization of these tumors and, more recently, I-131-MIBG has been used in trials in the treatment of pheochromocytoma, potentially giving rise to NET As a therapeutic target. However, because of varying levels or activities of the transporter, the ability of I-131-MIBG to be consistently incorporated into tumor cells is limited, and therefore various strategies to increase NET functional activity are being investigated, including the use of traditional chemotherapeutic agents such as cisplatin or doxorubicin. Other aspects of NET discussed in this short review include the regulation of the transporter and how novel protein-protein interactions between NET and structures such as syntaxin 1A may hold the key to innovative ways to increase the therapeutic value of I-131-MIBG.