Abnormal epithelial-mesenchymal interaction induces disordered HOX gene expression and enhances metastatic capacity

异常的上皮-间质相互作用诱导 HOX 基因表达紊乱并增强转移能力

• 批准号: 16390111
• 负责人: HAMADA Jun-ichi
• 金额: $ 9.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390111/
• 关键词: Homeobox; Epithelial-mesenchymal interaction; Hepatocyte growth factor (HGF); β-catenin; HOXB3; Transactivation; Invasion and metastasis; E-cadherin

Hepatocyte growth factor (HGF) is known as a mediator of epithelial cells and mesenchymal cells during morphogenesis in embryo. HOX genes act as master controller during the morphogenesis. Invasion and metastasis are considered to be a phenomenon caused from abnormal epithelial-mesenchymal interaction by morphogenesis-related factors including HGF. In this study, we aimed to demonstrate the hypothesis : HGF results in enhancement of invasion and metastasis by the altered expression of HOX genes which regulate metastasis-related genes. We obtained the following results. When human pancreatic cancer SUIT-2 cells were treated with HGF, E-cadhein, disappeared from cell membranes and β-catenin translocated from cell membrane to nucleus. Real-time quantitative RT-PCR analysis revealed that HGF increased the expression of only HOXB3 gene of 39 HOX genes. The results from luciferase reporter assays indicated that the complex of β-catenin and TCF/Lef1 transcription factor is bound to promoter region of HOXB3 gene and transactivates the gene. Cell biological studies showed that HGF promoted the cell scattering and motility of SUIT-2 cells. We are now analySing the phenotypical changes of SUIT-2 cells transfected with HOXB3 expression vectors to explore the genes of which expressions are regulated by HOXB3.

肝细胞生长因子（HGF）被认为是胚胎形态发生过程中上皮细胞和间充质细胞的介质。 HOX 基因在形态发生过程中充当主控制器。侵袭和转移被认为是由包括HGF在内的形态发生相关因子导致的上皮-间质相互作用异常引起的现象。在这项研究中，我们旨在证明以下假设：HGF 通过改变调节转移相关基因的 HOX 基因的表达来增强侵袭和转移。我们得到了以下结果。当人胰腺癌 SUIT-2 细胞用 HGF 处理时，E-钙粘蛋白从细胞膜上消失，β-连环蛋白从细胞膜转移到细胞核。实时定量RT-PCR分析显示，HGF仅增加39个HOX基因中HOXB3基因的表达。荧光素酶报告基因检测结果表明，β-catenin 和 TCF/Lef1 转录因子的复合物与 HOXB3 基因的启动子区域结合并反式激活该基因。细胞生物学研究表明，HGF 促进 SUIT-2 细胞的细胞分散和运动。我们现在正在分析HOXB3表达载体转染的SUIT-2细胞的表型变化，以探索HOXB3表达调控的基因。

项目成果

Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling(1).

通过基于 cDNA 阵列的表达谱预测胃癌患者的淋巴侵袭/淋巴结转移、复发和生存(1)。

• 发表时间: 2005
• 期刊: J. Surg. Res. 124
• 作者: Teramoto;K.
• 通讯作者: K.

Hypoxia suppresses the production of matrix metalloproteinases and migration human monocyte-derived dendritic cells.

缺氧抑制基质金属蛋白酶的产生和人单核细胞衍生的树突状细胞的迁移。

• 发表时间: 2005
• 期刊: Eur.J.Immunol. 35
• 作者: Zhao;W.
• 通讯作者: W.

Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system

• DOI: 10.1016/j.yexcr.2003.09.024
• 发表时间: 2004-02-01
• 期刊: EXPERIMENTAL CELL RESEARCH
• 影响因子: 3.7
• 作者: Takahashi, Y;Hamada, J;Moriuchi, T
• 通讯作者: Moriuchi, T

Hypoxia suppresses the production of matrix metalloproteinases and migration of human monocyte-derived dendritic cells.

缺氧会抑制基质金属蛋白酶的产生和人单核细胞衍生的树突状细胞的迁移。

• 发表时间: 2005
• 期刊: Eur.J.Immunol 35
• 作者: Zhao;W
• 通讯作者: W

連載講座 : 最近における癌遺伝子・抑制遺伝子の研究.肺癌・ヒト肺癌におけるHOX遺伝子の役割.

系列：癌基因和抑制基因的最新研究。HOX基因在肺癌和人类肺癌中的作用。

• 发表时间: 2006
• 期刊: Biotherapy 20
• 作者: Konishi;N.;Nakamura;M.;Ishida;E.;Shimada;K.;Mitsui;E.;Yoshikawa;R.;Yamamoto;H.;Tsujikawa;K.;浜田淳一
• 通讯作者: 浜田淳一