Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes
Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes
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DOI：
10.1016/j.neuropharm.2005.05.018
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Chen, S
中科院分区：
文献类型：
--
作者：
Marín, YE;Namkoong, J;Chen, S
黑色素瘤是黑色素细胞的异常增殖，黑色素细胞是皮肤中负责色素（黑色素）产生的细胞。在早期阶段，黑色素瘤可以通过手术切除并取得巨大成功，然而，由于对现有治疗方法缺乏反应，晚期黑色素瘤的死亡率很高。我们之前描述了一种小鼠黑色素瘤模型TG-3，该模型暗示了代谢性谷氨酸受体1 （Grm1，以前称为mGluR1）在黑色素瘤形成和转移中的异位表达[Pollock等，2003]。黑色素瘤小鼠模型提示代谢促谷氨酸信号在黑色素细胞瘤中的作用。[j].地理科学与技术。在这里，我们报告了来自独立小鼠黑色素瘤肿瘤的几种体外细胞系的特征。这些细胞系表现出转化黑色素细胞的特征表型，并表达Grm1和Grm5（另一种代谢性谷氨酸受体），以及麦克拉兰细胞特异性蛋白标记物。为了研究Grm5在小鼠体内黑色素瘤发展过程中的可能作用，我们将Grm5缺失的小鼠与TG-3杂交，产生了一种新的转基因小鼠，TGM。TGMs是Grm5的纯合子敲除，携带TG转基因，其发病、进展和转移与TG-3非常相似。综上所述，这些结果表明Grm1可以独立于Grm5的表达而在黑素细胞中作为癌基因。(c) 2005 Elsevier Ltd版权所有。
Melanoma is the aberrant proliferation of melanocytes, the cells in the skin responsible for pigment (melanin) production. In its early stages, melanoma can be surgically removed with great success, however, advanced stages of melanoma have a high mortality rate due to the lack of responsiveness to currently available therapies. We have previously characterized a mouse melanoma model, TG-3, which has implicated the ectopic expression of metabotropic glutamate receptor 1 (Grm1, formerly mGluR1), in melanomagenesis and metastasis [Pollock et al., 2003. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet. 34, 108-112.]. Here we report the characterization of several in vitro cell lines derived from independent mouse melanoma tumors. These cell lines show characteristic phenotypes of transformed melanocytes, and express Grm1, and Grm5 (another metabotropic glutamate receptor), as well as mclanocyte-specific protein markers. To investigate the possible role of Grm5 in vivo during melanoma development in our mice, we have crossed Grm5 null mice with TG-3, generating a new line of transgenic mice, TGM. TGMs, which are homozygote knockouts for Grm5 and carry the TG transgene, develop tumors with onset, progression, and metastasis very similar to that described for TG-3. Taken together, these results indicate that Grm1 can act as an oncogene in melanocytes independently of Grm5 expression. (c) 2005 Elsevier Ltd. All rights reserved.