Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
J Surg Res. 2013 Nov;185(1):255-63. doi: 10.1016/j.jss.2013.05.075. Epub 2013 Jun 11.
The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway.
The expression of TC-1 was immunohistochemically examined in 147 patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level.
TC-1 was detected in 97 of the 147 non-small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P < 0.01). In vitro experiments demonstrated that TC-1 expression affected both proliferation and invasion in the A549 cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathway's downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level.
TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors.
甲状腺癌-1（TC-1）或 c8orf4 基因编码一种 106 个残基的天然无序蛋白，已发现与甲状腺癌、胃癌和乳腺癌有关。最近的一项研究表明，该蛋白在人类乳腺癌的 Wnt/β-catenin 信号通路中起正向调节作用。然而，在肺癌领域尚未进行相关研究。因此，本研究旨在确认 TC-1、肺癌和 Wnt/β-catenin 信号通路之间的关系。
采用免疫组织化学方法检测 147 例非小细胞肺癌患者中 TC-1 的表达。采用慢病毒感染过表达和沉默 TC-1 的 A549 细胞，进行 MTT 细胞增殖分析，以及 Matrigel 侵袭实验和划痕实验，以确认不同 A549 细胞亚群的生物学行为变化。检测 Wnt/β-catenin 信号通路、关键基因β-catenin、血管内皮生长因子、周期蛋白 D1、基质金属蛋白酶-7、c-myc 和生存素的靶基因在 mRNA 和蛋白水平上的表达。
在 147 例非小细胞肺癌原发肿瘤标本中检测到 TC-1，其表达与 TNM 分期和区域淋巴结转移相关（P<0.01）。体外实验表明，TC-1 的表达影响 A549 细胞系的增殖和侵袭。此外，TC-1 蛋白的表达影响 Wnt/β-catenin 信号通路下游基因，如血管内皮生长因子和基质金属蛋白酶-7 的表达，在 mRNA 和蛋白水平上。
TC-1 的表达与肺癌侵袭性生物学行为相关，可能作为诱导这些行为的正向上游调节剂与 Wnt/β-catenin 通路协同作用。
