Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ann Surg Oncol. 2013 Sep;20(9):3140-50. doi: 10.1245/s10434-012-2474-4. Epub 2012 Jul 18.
Adaptor proteins, with multimodular structures, can participate in the regulation of various cellular functions. A novel adaptor protein XB130 has been implicated as a substrate and regulator of tyrosine kinase-mediated signaling and in controlling cell proliferation and apoptosis in thyroid and lung cancer cells. However, its expression and role in gastrointestinal cancer have not been investigated. We sought to determine the role of XB130 in cell cycle progression of esophageal squamous cell carcinoma (ESCC) cells and to examine its expression and effects on the prognosis of patients with ESCC.
Expression of XB130 in human ESCC cell lines was analyzed by Western blot testing and immunofluorescent staining. Knockdown experiments with XB130 small interfering RNA (siRNA) were conducted, and the effect on cell cycle progression was analyzed. Immunohistochemistry of XB130 for 52 primary tumor samples obtained from patients with ESCC undergoing esophagectomy was performed.
XB130 was highly expressed in TE2, TE5, and TE9 cells. In these cells, knockdown of XB130 with siRNA inhibited G1-S phase progression and increased the expression of p21, the cyclin-dependent kinase inhibitor. Immunohistochemistry showed that 71.2% of the patients expressed XB130 in the nuclei and/or cytoplasm of the ESCC cells. Further, nuclear expression of XB130 was an independent prognostic factor of postoperative survival.
These observations suggest that the expression of XB130 in ESCC cells may affect cell cycle progression and impact prognosis of patients with ESCC. A deeper understanding of XB130 as a mediator and/or biomarker in ESCC is needed.
衔接蛋白具有多模块结构，可参与多种细胞功能的调节。一种新型衔接蛋白 XB130 已被证实作为酪氨酸激酶介导的信号转导的底物和调节剂，并在甲状腺和肺癌细胞中控制细胞增殖和凋亡中发挥作用。然而，其在胃肠道癌症中的表达和作用尚未被研究。我们旨在确定 XB130 在食管鳞状细胞癌（ESCC）细胞周期进展中的作用，并研究其表达及其对 ESCC 患者预后的影响。
通过 Western blot 检测和免疫荧光染色分析人 ESCC 细胞系中 XB130 的表达。用 XB130 小干扰 RNA（siRNA）进行敲低实验，分析对细胞周期进展的影响。对 52 例接受食管癌切除术的 ESCC 患者的原发性肿瘤样本进行 XB130 的免疫组织化学检测。
TE2、TE5 和 TE9 细胞中高度表达 XB130。在这些细胞中，用 siRNA 敲低 XB130 抑制 G1-S 期进展并增加细胞周期蛋白依赖性激酶抑制剂 p21 的表达。免疫组化显示，71.2%的 ESCC 患者的细胞核和/或细胞质中表达 XB130。此外，XB130 的核表达是术后生存的独立预后因素。
这些观察结果表明，ESCC 细胞中 XB130 的表达可能影响细胞周期进程并影响 ESCC 患者的预后。需要更深入地了解 XB130 作为 ESCC 的介质和/或生物标志物的作用。
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