Reduced GNG2 expression levels in mouse malignant melanomas and human melanoma cell lines.
Reduced GNG2 expression levels in mouse malignant melanomas and human melanoma cell lines.
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发表时间：
2012
影响因子：
5.3
通讯作者：
I. Yajima;M. Kumasaka;Y. Naito;T. Yoshikawa;Hirokazu Takahashi;Y. Funasaka;Tamio Suzuki;Masashi Kato
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作者：
I. Yajima;M. Kumasaka;Y. Naito;T. Yoshikawa;Hirokazu Takahashi;Y. Funasaka;Tamio Suzuki;Masashi Kato
异三聚体G蛋白由Gα亚基和Gβγ二聚体组成。以往的研究表明，包括G-βγ-2亚单位在内的G-γ-二聚体与细胞的增殖、分化、侵袭和血管生成有关。然而，目前还没有关于Gng2/GNG2单独在任何一种肿瘤中表达水平的信息。在这项研究中，我们对来自RET转基因小鼠的良性黑素细胞瘤和恶性黑色素瘤(RET小鼠)进行了DNA微阵列分析。恶性黑色素瘤中Gng2转录表达水平低于良性肿瘤的1/10。在本研究检测的所有G蛋白γ亚基中，良性肿瘤和恶性黑色素瘤之间GNG2转录表达水平的差异最大。此外，与RET-小鼠良性黑素细胞瘤相比，恶性黑色素瘤中Gng2的蛋白表达水平降低。对人类恶性黑色素瘤的分析还显示，与正常人类上皮性黑素细胞(NHEM)的表达水平相比，GNG2在五个人类恶性黑色素瘤细胞系中的表达水平降低。因此，我们首次证明了GNG2/GNG2在恶性黑色素瘤中的表达水平降低，提示GNG2可能是恶性黑色素瘤的一个新的生物标志物。
Heterotrimeric G protein is composed of a Gα-subunit and a Gβγ-dimer. Previous studies have revealed that Gβγ-dimers including the Gγ2 subunit (Gng2/GNG2) are associated with cell proliferation, differentiation, invasion and angiogenesis. At present, however, there is no information on the expression level of Gng2/GNG2 alone in any kind of tumor. In this study, we performed DNA microarray analysis in a benign melanocytic tumor and a malignant melanoma from RET-transgenic mice (RET-mice). Gng2 transcript expression levels in a malignant melanoma were less than 1/10 of the level in a benign tumor. The difference in Gng2 transcript expression levels between benign tumors and malignant melanomas was greatest among all of the G protein γ subunits examined in this study. Moreover, protein expression levels of Gng2 were decreased in malignant melanomas compared with those in benign melanocytic tumors in RET-mice. Analysis of human malignant melanomas also showed reduced GNG2 protein expression levels in five human malignant melanoma cell lines compared with the expression levels in normal human epithelial melanocytes (NHEM). Thus, we demonstrated for the first time that Gng2/GNG2 expression levels are reduced in malignant melanoma, suggesting that GNG2 could be a novel biomarker for malignant melanoma.