AKT2 is a downstream target of metabotropic glutamate receptor 1 (Grm1).
AKT2 is a downstream target of metabotropic glutamate receptor 1 (Grm1).
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AKT2是代谢型谷氨酸受体1（GRM1）的下游靶标。
DOI：
10.1111/j.1755-148x.2009.00648.x
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发表时间：
2010-02
影响因子：
4.3
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Shin SS;Wall BA;Goydos JS;Chen S
我们之前通过证明稳定的Grm1 - 小鼠黑素细胞克隆在体外缺乏生长补充剂和贴壁的情况下增殖，报道了Grm1的致癌特性。此外，这些克隆在体内也表现出侵袭性的致瘤表型，在免疫缺陷小鼠和同基因小鼠中肿瘤形成的潜伏期都很短。我们还检测到同种异体移植肿瘤中AKT的强烈激活，特别是AKT2是主要涉及的异构体。同时，我们评估了几个人类黑色素瘤活检样本，再次发现AKT2是这些人类黑色素瘤活检样本中主要被激活的AKT。在培养的稳定的Grm1 - 小鼠黑素细胞克隆以及一个表达mGlu1的人类黑色素瘤细胞系C8161中，其激动剂对mGlu1的刺激导致AKT的激活，而用mGlu1拮抗剂预孵育则消除了mGlu1激动剂诱导的AKT激活。此外，在存在小干扰AKT2 RNA（siAKT2）的情况下，检测到Grm1 - 小鼠黑素细胞同种异体移植物的肿瘤体积减小。综上所述，这些结果表明，除了之前报道的MAPK途径是受刺激的mGlu1的下游靶点外，AKT2是Grm1介导的黑素细胞转化中的另一个下游靶点。
We reported earlier on the oncogenic properties of Grm1 by demonstrating that stable Grm1-mouse-melanocytic clones proliferate in the absence of growth supplement and anchorage in vitro. In addition these clones also exhibit aggressive tumorigenic phenotypes in vivo with short latency in tumor formation in both immunodeficient and syngeneic mice. We also detected strong activation of AKT in allograft tumors specifically AKT2 as the predominant isoform involved. In parallel we assessed several human melanoma biopsy samples and found again that AKT2 was the predominantly activated AKT in these human melanoma biopsies. In cultured stable Grm1-mouse melanocytic clones, as well as an mGlu1 expressing human melanoma cell line, C8161, stimulation of mGlu1 by its agonist led to the activation of AKT, while pre-incubation with mGlu1-antagonist abolished mGlu1-agonist-induced AKT activation. In addition, a reduction in tumor volume of Grm1-mouse-melanocytic-allografts was detected in the presence of small interfering AKT2 RNA (siAKT2). Taken together, these results showed that, in addition to the MAPK pathway previously reported being a downstream target of stimulated mGlu1, AKT2 is another downstream target in Grm1 mediated melanocyte transformation.