Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 200072 Shanghai, China.
Dig Dis Sci. 2011 Jun;56(6):1645-55. doi: 10.1007/s10620-010-1510-0. Epub 2010 Dec 4.
The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now.
To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis.
Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line.
The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001).
Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.
细胞 E1A 刺激基因的抑制剂（CREG）是一种分泌型糖蛋白，已经在人胚胎癌细胞、血管平滑肌细胞和 NIH3T3 成纤维细胞中进行了研究。然而，直到现在，它与人类胃癌（GC）细胞增殖和转移的关系还没有在 GC 中进行研究。
研究 CREG 在 GC 中的表达及其与 GC 细胞增殖和转移的关系。
使用 42 例 GC 组织、匹配的正常胃组织以及人胃癌细胞系 BGC-823、SGC-7901、MKN45、正常胃黏膜细胞系 GES 和 HUVEC 细胞系 ECV304 分析 CREG 在 mRNA 和蛋白水平上的表达。然后通过免疫组织化学方法在 42 例 GC 组织中进一步检测 CREG 的表达，并评估 CREG 水平与病理和临床数据之间的相关性。最后，我们使用特异性 siRNA 下调 GC 细胞中 CREG 的表达，评估 CREG 在 GC 细胞系增殖和转移/侵袭中的作用。
与相邻正常组织和正常胃细胞相比，恶性 GC 组织和细胞中的 CREG 水平更高（p < 0.001）。此外，CREG 的表达水平与肿瘤临床分期（p = 0.001）、肿瘤转移（p < 0.001）和肿瘤浸润分期（p = 0.019）呈正相关。此外，通过使用 siRNA，我们发现下调 CREG 的表达抑制了 GC 细胞的增殖（p < 0.05），以及 GC 细胞的迁移（p = 0.001）。
我们的数据表明，CREG 在胃癌细胞增殖和转移中发挥重要作用，CREG 可能是 GC 的一个潜在治疗靶点。
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