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）是胚胎发育过程中上皮细胞和间充质细胞的调节因子。HOX基因在形态发生中起着主控制者的作用。侵袭和转移被认为是由包括HGF在内的形态发生相关因子引起的异常上皮-间质相互作用的现象。在这项研究中，我们的目的是证明这样的假设：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。用HGF处理人胰腺癌SUIT-2细胞后，E-cadhein从细胞膜上消失，β-catenin从细胞膜转位到细胞核。实时荧光定量RT-PCR分析显示，HGF仅增加了39个HOX基因中HOXB 3基因的表达。荧光素酶报告基因检测结果表明，β-catenin与TCF/Lef 1转录因子的复合物结合于HOXB 3基因的启动子区，并对HOXB 3基因起反式激活作用。细胞生物学研究表明，HGF可促进SUIT-2细胞的分散和运动。我们现在正在分析HOXB 3表达载体转染SUIT-2细胞的表型变化，以探索HOXB 3调控表达的基因。

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

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

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