Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma
Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma
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DOI：
10.1038/onc.2008.329
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发表时间：
2008-12-01
期刊：
影响因子：
8
通讯作者：
Aiba, A.
中科院分区：
文献类型：
--
作者：
Ohtani, Y.;Harada, T.;Aiba, A.
小鼠黑素细胞中代谢型谷氨酸受体亚型1（mGluR 1）的异位表达诱导黑色素瘤形成。虽然已经证明了mGluR 1在黑色素瘤初始阶段的发展中的需要，但其在体内黑色素瘤生长中的作用仍不清楚。在这项研究中，我们开发了新的转基因小鼠，有条件地表达mGluR 1的黑素细胞，使用四环素调控系统。转基因小鼠的耳朵和尾巴上的色素病变开始出现后29周的mGluR 1转基因的激活，和转基因小鼠产生黑色素瘤的频率为100%转基因激活后52周。随后失活的mGluR 1转基因在黑色素瘤荷瘤小鼠抑制黑色素瘤的生长与磷酸化ERK 1/2的免疫反应性降低，而小鼠与持续表达的mGluR 1开发更大的黑色素瘤负担。因此，mGluR 1表达不仅是黑色素瘤发展所必需的，而且也是体内黑色素瘤生长所必需的。这些研究结果表明，黑色素瘤的生长可以在体内抑制消除肿瘤发生中涉及的多种遗传异常之一。
Ectopic expression of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse melanocytes induces melanoma formation. Although requirement of mGluR1 for development of melanoma in the initial stage has been demonstrated, its role in melanoma growth in vivo remains unclear. In this study, we developed novel transgenic mice that conditionally express mGluR1 in melanocytes, using a tetracycline regulatory system. Pigmented lesions on the ears and tails of the transgenic mice began to appear 29 weeks after activation of the mGluR1 transgene, and the transgenic mice produced melanomas at a frequency of 100% 52 weeks after transgene activation. Subsequent inactivation of the mGluR1 transgene in melanoma-bearing mice inhibited melanoma growth with reduction of immunoreactivity to phosphorylated ERK1/2, whereas mice with persistent expression of mGluR1 developed larger melanoma burdens. mGluR1 expression is thus required not only for melanoma development but also for melanoma growth in vivo. These findings suggest that growth of melanoma can be inhibited in vivo by eliminating only one of the multiple genetic anomalies involved in tumorigenesis.