Wang Lili, Ma Jian, Li Jiang, Li Xiaoling, Zhang Qiuhong, Peng Shuping, Peng Cong, Zhou Ming, Xiong Wei, Yang Jianbo, Zhou Jie, Fan Songqing, Tan Chen, Yan Qun, Shen Shourong, Li Guiyuan
Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
J Cell Biochem. 2005 May 1;95(1):64-73. doi: 10.1002/jcb.20393.
Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. A novel NPC-related gene was isolated by location candidate cloning strategy, whose expression was down-regulated in NPC. This gene was designated human NGX6 (Genbank accession AF188239) and encoded a predicted protein of 338 amino acids that harbors an EGF-like domain. The effects of NGX6 on cells from human NPC cell line HNE1 were investigated. The cells transfected with NGX6 had a markedly high expression of NGX6, leading to significant decrease in cell proliferation and the capability to form colonies in soft agar, delaying the G0-G1 cell cycle progression. Flow cytometry assay indicated that the expression of cyclin D1 significantly decreased in NGX6-transfected HNE1 cells as well as cyclin A and E. There was a delay in tumor formation and a dramatic reduction in tumor size when cells transfected with NGX6 were injected into nude mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK pathway. We propose that NGX6, as an EGF-like domain gene, could delay cell cycle G0-G1 progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.
鼻咽癌（NPC）在中国南方是一种常见癌症，但在世界其他地区较为罕见。通过定位候选克隆策略分离出一个新的鼻咽癌相关基因，其在鼻咽癌中表达下调。该基因被命名为人NGX6（Genbank登录号AF188239），编码一个预测的含338个氨基酸的蛋白质，该蛋白质含有一个表皮生长因子（EGF）样结构域。研究了NGX6对人鼻咽癌细胞系HNE1细胞的影响。转染NGX6的细胞中NGX6表达明显升高，导致细胞增殖及在软琼脂中形成集落的能力显著降低，使G0-G1期细胞周期进程延迟。流式细胞术检测表明，在转染NGX6的HNE1细胞中，细胞周期蛋白D1以及细胞周期蛋白A和E的表达均显著降低。将转染NGX6的细胞注射到裸鼠体内时，肿瘤形成延迟且肿瘤大小显著减小。另一方面，我们发现NGX6在表皮生长因子受体（EGFR）Ras/丝裂原活化蛋白激酶（Mek）/丝裂原活化蛋白激酶（MAPK）信号通路中起负性作用。我们提出，NGX6作为一个含EGF样结构域的基因，可通过负性调节鼻咽癌细胞中的EGFR信号通路并下调细胞周期蛋白D1和E的表达，从而延迟细胞周期G0-G1进程，进而抑制细胞增殖。
