Park Yo Seph, Nemeño Judee Grace E, Choi Na Young, Lee Jeong Ik, Ko Kisung, Choi Seung-Cheol, Kim Wan Seop, Han Dong Wook, Tapia Natalia, Ko Kinarm
Biol Chem. 2016 Mar;397(3):249-55. doi: 10.1515/hsz-2015-0255.
Key regulatory genes in pluripotent stem cells are of interest not only as reprogramming factors but also as regulators driving tumorigenesis. Nanog is a transcription factor involved in the maintenance of embryonic stem cells and is one of the reprogramming factors along with Oct4, Sox2, and Lin28. Nanog expression has been detected in different types of tumors, and its expression is a poor prognosis for cancer patients. However, there is no clear evidence that Nanog is functionally involved in tumorigenesis. In this study, we induced overexpression of Nanog in mouse embryonic fibroblast cells and subsequently assessed their morphological changes, proliferation rate, and tumor formation ability. We found that Nanog overexpression induced immortalization of mouse embryonic fibroblast cells (MEFs) and increased their proliferation rate in vitro. We also found that formation of tumors after subcutaneous injection of retroviral-Nanog infected MEFs (N-MEFs) into athymic mouse. Cancer-related genes such as Bmi1 were expressed at high levels in N-MEFs. Hence, our results demonstrate that Nanog is able to transform normal somatic cells into tumor cells.
多能干细胞中的关键调控基因不仅作为重编程因子备受关注，还作为驱动肿瘤发生的调节因子受到重视。Nanog是一种参与维持胚胎干细胞的转录因子，它与Oct4、Sox2和Lin28一样，是重编程因子之一。已在不同类型的肿瘤中检测到Nanog的表达，其表达对癌症患者而言预后较差。然而，尚无明确证据表明Nanog在功能上参与肿瘤发生。在本研究中，我们在小鼠胚胎成纤维细胞中诱导Nanog过表达，随后评估其形态变化、增殖率和肿瘤形成能力。我们发现，Nanog过表达诱导小鼠胚胎成纤维细胞（MEFs）永生化，并在体外提高其增殖率。我们还发现，将逆转录病毒-Nanog感染的MEFs（N-MEFs）皮下注射到无胸腺小鼠后会形成肿瘤。诸如Bmi1等癌症相关基因在N-MEFs中高表达。因此，我们的结果表明，Nanog能够将正常体细胞转化为肿瘤细胞。
