Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongdajie Street, Fengtai, Beijing 100071, People's Republic of China.
Mol Cell Biochem. 2011 May;351(1-2):109-16. doi: 10.1007/s11010-011-0717-5. Epub 2011 Jan 19.
Tumor development has long been known to resemble abnormal embryogenesis. The ESC self-renewal gene NANOG is purportedly expressed in some epithelial cancer cells and solid tumors, but a casual role in tumor development has remained unclear. In order to more comprehensively elucidate the relationship between human Nanog and tumorigenesis, the hNanog was ectopically expressed in the 293 cell line to investigate its potential for malignant transformation of cells both in vitro and in vivo. Here we provide compelling evidence that the overexpression of hNanog resulted in increased cell proliferation, anchor-independent growth in soft agar, and formation of tumors after subcutaneous injection of athymic nude mice. Pathologic analysis revealed that these tumors were poorly differentiated. In analysis of the underlying molecular mechanism, two proteins, FAK and Ezrin, were identified to be upregulated in the hNanog expressing 293 cells. Our results demonstrate that hNanog is a potent human oncogene and has the ability to induce cellular transformation of human cells.
肿瘤的发生长期以来被认为类似于异常的胚胎发生。ESC 自我更新基因 NANOG 据称在一些上皮癌细胞和实体肿瘤中表达，但在肿瘤发生中的偶然作用仍不清楚。为了更全面地阐明人类 Nanog 与肿瘤发生之间的关系，我们将 hNanog 异位表达于 293 细胞系中，以研究其在体外和体内对细胞恶性转化的潜在作用。在这里，我们提供了令人信服的证据表明，hNanog 的过表达导致细胞增殖增加、软琼脂中无锚定生长以及皮下注射裸鼠后形成肿瘤。病理分析显示这些肿瘤分化不良。在对潜在分子机制的分析中，鉴定出两种蛋白质，FAK 和 Ezrin，在表达 hNanog 的 293 细胞中上调。我们的结果表明，hNanog 是一种有效的人类致癌基因，具有诱导人类细胞的细胞转化的能力。
