Department of Surgery, Beppu Hospital, Kyushu University, Beppu, Oita 874-0838, Japan.
Oncol Rep. 2013 Oct;30(4):1971-5. doi: 10.3892/or.2013.2664. Epub 2013 Aug 8.
Previous studies have suggested conflicting roles for the E3 ubiquitin ligase COP1 in tumorigenesis, providing evidence that both the oncoprotein c-Jun and the tumor suppressor p53 may be COP1 targets. In the present study, we focused on the clinical significance of COP1 expression in gastric cancer cases and analyzed the malignant behavior of COP1‑knockdown gastric cancer cells in vitro. We analyzed COP1 expression in cancer lesions and the corresponding normal mucosa to demonstrate the clinical significance of COP1 expression in 133 cases of gastric cancer. We also investigated the relationship between COP1 expression and cell proliferation and the association of COP1 with c‑Jun transcriptional target genes, such as MMP1, MMP7 and MMP10. The expression of COP1 mRNA was significantly lower in gastric cancer tissues compared to the corresponding normal mucosa (P=0.049). In multivariate analysis for overall survival, we found that COP1 expression was an independent prognostic factor in gastric cancer. Knockdown of COP1 expression in the gastric cancer cell lines MKN‑45 and NUGC4 promoted proliferation, and significant associations between COP1 expression and MMP1, MMP7 and MMP10 were also observed in knockdown assays. In conclusion, the present study suggests that loss of COP1 expression may be a novel indicator for the biological aggressiveness in gastric cancer.
先前的研究表明 E3 泛素连接酶 COP1 在肿瘤发生中的作用相互矛盾，为癌蛋白 c-Jun 和肿瘤抑制因子 p53 可能都是 COP1 靶标提供了证据。在本研究中，我们专注于 COP1 在胃癌病例中的表达的临床意义，并分析了体外 COP1 敲低胃癌细胞的恶性行为。我们分析了癌症病变和相应的正常黏膜中的 COP1 表达，以证明 COP1 在 133 例胃癌中的表达的临床意义。我们还研究了 COP1 表达与细胞增殖之间的关系，以及 COP1 与 c-Jun 转录靶基因（如 MMP1、MMP7 和 MMP10）之间的关联。与相应的正常黏膜相比，胃癌组织中的 COP1 mRNA 表达显著降低（P=0.049）。在总生存期的多变量分析中，我们发现 COP1 表达是胃癌的一个独立预后因素。在胃癌细胞系 MKN-45 和 NUGC4 中敲低 COP1 表达促进了增殖，并且在敲低实验中还观察到 COP1 表达与 MMP1、MMP7 和 MMP10 之间存在显著关联。综上所述，本研究表明 COP1 表达缺失可能是胃癌生物学侵袭性的一个新指标。
