REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION (RT-PCR) ANALYSIS OF MONOAMINE TRANSPORTERS IN NEUROBLASTOMA CELL-LINES - CORRELATIONS TO METAIODOBENZYLGUANIDINE (MIBG) UPTAKE AND TYROSINE-HYDROXYLASE GENE-EXPRESSION
REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION (RT-PCR) ANALYSIS OF MONOAMINE TRANSPORTERS IN NEUROBLASTOMA CELL-LINES - CORRELATIONS TO METAIODOBENZYLGUANIDINE (MIBG) UPTAKE AND TYROSINE-HYDROXYLASE GENE-EXPRESSION
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DOI：
10.1016/0959-8049(95)00039-l
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发表时间：
1995-01-01
影响因子：
8.4
通讯作者：
BECK, J
中科院分区：
文献类型：
--
作者：
LODE, HN;BRUCHELT, G;BECK, J
放射性标记间碘苄胍（MIBG）已广泛用于神经母细胞瘤患者的放射性造影和靶向放射治疗。最近，已经证明MIBG通过去甲肾上腺素转运蛋白掺入成神经细胞瘤细胞中。在本研究中对SK-N-SH人神经母细胞瘤细胞进行的体外实验表明，MIBG的摄取受到去甲肾上腺素的抑制，多巴胺的抑制程度更高，5-羟色胺的抑制程度更低，这表明相应的转运蛋白也可能有助于MIBG的摄取。然而，多巴胺和5-羟色胺转运蛋白基因表达均未检测到。去甲肾上腺素转运蛋白基因的表达被发现在4的6个调查的细胞系，这与特定的MIBG摄取。此外，去甲肾上腺素转运蛋白和酪氨酸羟化酶的基因表达，儿茶酚胺合成的关键调控酶，观察到负相关。这些数据表明，MIBG是专门纳入只有在神经母细胞瘤细胞，其中有去甲肾上腺素转运蛋白基因表达。此外，神经母细胞瘤细胞中的儿茶酚胺状态受儿茶酚胺合成和再摄取系统的关键元件的协调表达调节。
Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.