Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation
Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation
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DOI：
10.1111/j.1755-148x.2008.00452.x
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发表时间：
2008-06-01
影响因子：
4.3
通讯作者：
Chen, Suzie
中科院分区：
文献类型：
--
作者：
Shin, Seung-Shick;Namkoong, Jin;Chen, Suzie
以前，我们报道了一个转基因小鼠系，TG-3，发展自发性黑色素瘤与100%的转移率。我们证明了Grm 1在黑素细胞中的异位表达足以在体内诱导黑色素瘤。在本研究中，Grm 1在两个培养的永生化黑素细胞中的转化特性进行了研究。我们发现，与亲本黑素细胞相反，这些Grm 1克隆已经失去了TPA补充增殖的需要，并获得了在半固体培养基中形成集落的能力。这些细胞的异种移植物在免疫缺陷裸鼠和同基因小鼠中均形成了具有短潜伏期（3-5天）的稳健肿瘤。这些细胞的恶性表现为血管生成和对肌肉和肠的侵袭。通过诱导型siRNA系统证明了Grm 1表达对维持转化的需要。与对照组相比，诱导Grm 1的siRNA表达减少了体外增殖/存活细胞的数量，并抑制了体内异种移植肿瘤的生长。总之，这些结果表明，外源引入的Grm 1的表达足以诱导永生化黑素细胞的完全转化。
Previously, we reported a transgenic mouse line, TG-3, that develops spontaneous melanoma with 100% penetrance. We demonstrated that ectopic expression of Grm1 in melanocytes was sufficient to induce melanoma in vivo. In this present study, the transforming properties of Grm1 in two cultured immortalized melanocytes were investigated. We showed that, in contrast to parental melanocytes, these Grm1-clones have lost their requirement of TPA supplement for proliferation and have acquired the ability to form colonies in semi-solid medium. Xenografts of these cells formed robust tumors in both immunodeficient nude and syngeneic mice with a short latency (3-5 days). The malignancy of these cells was demonstrated by angiogenesis and invasion to the muscle and the intestine. The requirement of Grm1 expression for the maintenance of transformation was demonstrated by an inducible siRNA system. Induction of expression of siRNA for Grm1 reduced the number of proliferating/viable cells in vitro and suppressed in vivo xenografted tumor growth in comparison with control. Taken together, these results showed that expression of exogeneously introduced Grm1 is sufficient to induce full transformation of immortalized melanocytes.