甲状腺刺激素胚胎因子在膀胱癌中下调，并通过 AKT/FOXOs 信号通路抑制增殖和肿瘤发生。
Thyrotroph embryonic factor is downregulated in bladder cancer and suppresses proliferation and tumorigenesis via the AKT/FOXOs signalling pathway.
机构信息
Department of Urologic Oncosurgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Key Laboratory of Protein Modification and Degradation, the Department of Pathophysiology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
出版信息
Cell Prolif. 2019 Mar;52(2):e12560. doi: 10.1111/cpr.12560. Epub 2018 Dec 4.
OBJECTIVES
Thyrotroph embryonic factor (TEF) plays an important role in several different processes in normal human cells; however, its function in malignant cells has not been fully elucidated.
MATERIALS AND METHODS
The mRNA levels of TEF in 408 bladder cancer (BC) samples from the Cancer Genome Atlas (TCGA) database were analysed in depth. Next, the expression of TEF in 7 BC cell lines was compared to that in normal bladder epithelial cells. The cell count, colony formation and anchorage-independent growth assays as well as a nude mouse xenograft model were utilized to examine the effects of TEF on proliferation and tumorigenesis. Immunofluorescence staining, flow cytometry analysis and treatment with an AKT inhibitor were performed to explore the molecular regulation mechanisms of TEF in BC.
RESULTS
Analysis of TCGA data indicated that TEF mRNA was decreased in BC samples compared to that in normal bladder epithelial cells and correlated with the poor survival of BC patients. Additional experiments verified that the mRNA and protein expression of TEF were significantly decreased in BC cells compared to that in normal bladder epithelial cells. Upregulation of TEF expression significantly retarded BC cell growth by inhibiting the G1/S transition via regulating AKT/FOXOs signalling.
CONCLUSION
Our results suggest that TEF might play an important role in suppressing BC cells proliferation and tumorigenesis.
目的
甲状腺细胞滋养因子（TEF）在正常人体细胞的多个不同过程中发挥重要作用；然而，其在恶性细胞中的功能尚未完全阐明。
材料与方法
深入分析了癌症基因组图谱（TCGA）数据库中 408 例膀胱癌（BC）样本中 TEF 的 mRNA 水平。接下来，比较了 7 种 BC 细胞系与正常膀胱上皮细胞中 TEF 的表达。利用细胞计数、集落形成和无锚定独立生长测定以及裸鼠异种移植模型来检测 TEF 对增殖和致瘤性的影响。通过免疫荧光染色、流式细胞术分析和 AKT 抑制剂处理，探讨了 TEF 在 BC 中的分子调控机制。
结果
TCGA 数据分析表明，与正常膀胱上皮细胞相比，BC 样本中 TEF mRNA 减少，且与 BC 患者的不良预后相关。进一步的实验验证了 TEF 在 BC 细胞中的 mRNA 和蛋白表达均明显低于正常膀胱上皮细胞。上调 TEF 表达通过调节 AKT/FOXOs 信号通路抑制 G1/S 期转换，显著抑制 BC 细胞生长。
结论
我们的研究结果表明，TEF 可能在抑制 BC 细胞增殖和致瘤性方面发挥重要作用。
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