N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma
N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma
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DOI：
10.1158/1078-0432.ccr-03-0262
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发表时间：
2004-09-01
影响因子：
11.5
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Yoshinaga, K;Inoue, H;Mori, M
目的：激活素A是转化生长因子β超家族的成员，在胚胎干细胞的分化中发挥重要作用。我们之前报道过激活素A的表达与食管癌的淋巴结转移有关，我们当前工作的目的是阐明激活素A高表达的肿瘤侵袭行为的分子机制。 实验设计：我们使用激活素A的亚基激活素βA稳定转染的人食管癌细胞系与对照人食管癌细胞系的基因表达谱进行了比较。 cDNA微阵列。结果：我们发现转染子中神经元钙粘蛋白（N-cadherin）的表达水平高于对照细胞。无论上皮钙粘蛋白（E-cadherin）的表达如何，N-钙粘蛋白均位于转染子的细胞表面，并且食管癌临床样本中N-钙粘蛋白mRNA的表达与激活素βA mRNA的表达显着相关（n = 51；r = 0.855）。临床病理分析提示，N-cadherin mRNA表达与瘤壁浸润深度相关，N-cadherin mRNA高表达组患者预后明显差于N-cadherin低表达组患者（P = 0.046）。结论：这些结果表明，激活素A可能介导N-cadherin表达，这可能与浸润深度和不良预后有关。
Purpose: Activin A is a member of the transforming growth factor beta superfamily and plays an important role in the differentiation of embryonic stem cells. We have reported previously that the expression of activin A is associated with lymph node metastasis in esophageal cancer, and our purpose in the current work is to clarify the molecular mechanism of the aggressive behavior of tumors that have high activin A expression.Experimental Design: We have compared the gene expression profiles of human esophageal carcinoma cell lines that were stably transfected with activin betaA, which is a subunit of activin A, with those of control human esophageal carcinoma cell lines, using a cDNA microarray.Results: We found that the expression level of neuronal cadherin (N-cadherin) was higher in the transfectants than in the control cells. N-cadherin was located on the cell surface of the transfectants, irrespective of the expression of epithelial cadherin (E-cadherin), and the expression of N-cadherin mRNA was significantly associated with that of activin betaA mRNA in clinical samples of esophageal carcinoma (n = 51; r = 0.855). A clinicopathologic analysis suggested that expression of N-cadherin mRNA was associated with the depth of tumor wall invasion, and a group of patients with high expression of N-cadherin mRNA showed a significantly poorer prognosis than a group of patients with low N-cadherin expression (P = 0.046).Conclusions: These results indicate that activin A might mediate the expression of N-cadherin and that this may be associated with depth of invasion and poor prognosis.