Xu Wenwen, Gu Junjie, Ren Qingling, Shi Yanqiu, Xia Qinhua, Wang Jing, Wang Suli, Wang Yingchun, Wang Jinhua
Department of Gynaecology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 55 Hanzhong Road, Nanjing, 210029, China.
Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, 42 Baiziting, Nanjing, 210009, China.
Tumour Biol. 2016 Apr;37(4):4493-500. doi: 10.1007/s13277-015-4245-x. Epub 2015 Oct 26.
It has been reported that nuclear factor of activated T cells (NFATC1) was up-regulated in cancers mediating malignant behaviors. However, the role of NFATC1 in ovarian cancer has not been elucidated. In the present study, we undertook to explore the clinicopathological significance of NFATC1 expression and the mechanism by which NFATC1 works in ovarian cancer. Expression status of NFATC1 was examined using immunohistochemistry. Both knockdown and re-expression of NFATC1 on ovarian cancer cells were employed to observe the effect overgrowth. It was found that NFATC1 was significantly overexpressed in ovarian cancer tissues in comparison with paired normal control tissues and that overexpression of NFATC1 was significantly associated with metastasis and poor prognosis on clinical tissue level. In in vitro ovarian cancer cell lines, we found that NFATC1 can promote proliferation up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway. Together, the results we obtained demonstrated that NFATC1 played oncogenic role in ovarian cancer. Mechanistically, NFATC1 promoted growth of ovarian cancer cells up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway, suggesting that NFATC1 might be used as a therapeutic target for ovarian cancer.
据报道，活化T细胞核因子（NFATC1）在介导恶性行为的癌症中上调。然而，NFATC1在卵巢癌中的作用尚未阐明。在本研究中，我们试图探讨NFATC1表达的临床病理意义以及NFATC1在卵巢癌中发挥作用的机制。采用免疫组织化学法检测NFATC1的表达状态。通过对卵巢癌细胞进行NFATC1的敲低和重新表达来观察其对细胞过度生长的影响。结果发现，与配对的正常对照组织相比，NFATC1在卵巢癌组织中显著过表达，并且在临床组织水平上，NFATC1的过表达与转移及不良预后显著相关。在体外卵巢癌细胞系中，我们发现NFATC1可通过激活ERK1/2/p38/MAPK信号通路上调c-myc从而促进细胞增殖。总之，我们获得的结果表明NFATC1在卵巢癌中发挥致癌作用。机制上，NFATC1通过激活ERK1/2/p38/MAPK信号通路上调c-myc促进卵巢癌细胞生长，提示NFATC1可能作为卵巢癌的治疗靶点。
