Kawamata Hitoshi, Furihata Tadashi, Omotehara Fumie, Sakai Taro, Horiuchi Hideki, Shinagawa Yasuhiro, Imura Johji, Ohkura Yasuo, Tachibana Masatsugu, Kubota Keiichi, Terano Akira, Fujimori Takahiro
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Mibu, Shimo-Tsuga, Tochigi 321-0293, Japan.
Cancer Sci. 2003 Aug;94(8):699-706. doi: 10.1111/j.1349-7006.2003.tb01505.x.
We isolated a metastasizing human esophageal squamous cell carcinoma (SCC) cell line, T.Tn-AT1, from a parental non-metastasizing cell line, T.Tn, by in vitro selection and by use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in T.Tn-AT1 and T.Tn by cDNA microarray analysis. The gene expression profiles of T.Tn and T.Tn-AT1 were very similar, and only 34 genes showed more than 3-fold differential expression. Among the 34 genes, 29 genes were down-regulated and only 5 genes were up-regulated in T.Tn-AT1 cells. Subsequently, we confirmed the expression levels of 14 of the 34 genes in T.Tn and T.Tn-AT1 cells by means of reverse transcription-polymerase chain reaction. The expression of 8 genes (KAL1, HPGD, NDN, REG1A, CXCR4, SPOCK, DIAPH2 and AIF1) was down-regulated and that of one gene (VNN2) was up-regulated in T.Tn-AT1 cells. These 9 genes encoded proteins associated with metastatic processes, such as adhesion, migration, inflammation, proliferation, and differentiation. Thus, these genes might regulate the metastasis of esophageal SCC, and could be predictive markers for lymph node metastasis of esophageal SCC.
我们通过体外筛选并利用裸鼠原位接种模型，从亲代非转移细胞系T.Tn中分离出一种转移性人食管鳞状细胞癌（SCC）细胞系T.Tn-AT1。然后，我们通过cDNA微阵列分析比较了T.Tn-AT1和T.Tn中9206个基因的表达谱。T.Tn和T.Tn-AT1的基因表达谱非常相似，只有34个基因表现出超过3倍的差异表达。在这34个基因中，T.Tn-AT1细胞中有29个基因下调，只有5个基因上调。随后，我们通过逆转录-聚合酶链反应证实了T.Tn和T.Tn-AT1细胞中34个基因中的14个基因的表达水平。在T.Tn-AT1细胞中，8个基因（KAL1、HPGD、NDN、REG1A、CXCR4、SPOCK、DIAPH2和AIF1）的表达下调，1个基因（VNN2）的表达上调。这9个基因编码与转移过程相关的蛋白质，如黏附、迁移、炎症、增殖和分化。因此，这些基因可能调节食管SCC的转移，并可能成为食管SCC淋巴结转移的预测标志物。
