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

基本信息

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

项目摘要

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）被称为胚胎形态发生过程中上皮细胞和间质细胞的介体。 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异常发生与形态发生相关的因子在内的异常上皮 - 间质相互作用引起的现象，包括HGF。在这项研究中，我们旨在证明以下假设：HGF通过调节转移相关基因的HOX基因的表达改变导致侵袭和转移的增强。我们获得了以下结果。当人胰腺癌诉讼2细胞用HGF治疗时，e-Cadhein从细胞膜中消失，而从细胞膜转移到核us的细胞膜和β-catenin。实时定量RT-PCR分析表明，HGF仅增加了39个HOX基因的HOXB3基因的表达。荧光素酶报告基因测定的结果表明，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基因。细胞生物学研究表明，HGF促进了西装2细胞的细胞散射和运动。现在，我们正在分析用HOXB3表达载体翻译的西装-2细胞的表型变化，以探索表达受HOXB3调节的基因。

项目成果

期刊论文数量（40）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer.

DOI：
10.1016/j.jss.2004.06.002
发表时间：
2004-11
期刊：
The Journal of surgical research
影响因子：
0
作者：
M. Takada;M. Tada;Eiji Tamoto;Akiko Kawakami;Katsuhiko Murakawa;G. Shindoh;Ken-ichi Teramoto;A. Matsunaga;K. Komuro;M. Kanai;Y. Fujiwara;K. Shirata;Norihiro Nishimura;M. Miyamoto;S. Okushiba;S. Kondo;J. Hamada;H. Katoh;T. Yoshiki;T. Moriuchi
通讯作者：
M. Takada;M. Tada;Eiji Tamoto;Akiko Kawakami;Katsuhiko Murakawa;G. Shindoh;Ken-ichi Teramoto;A. Matsunaga;K. Komuro;M. Kanai;Y. Fujiwara;K. Shirata;Norihiro Nishimura;M. Miyamoto;S. Okushiba;S. Kondo;J. Hamada;H. Katoh;T. Yoshiki;T. Moriuchi

Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines.

DOI：
10.3892/ijo.25.5.1415
发表时间：
2004-11
期刊：
International journal of oncology
影响因子：
5.2
作者：
A. Tsutsumida;J. Hamada;M. Tada;T. Aoyama;K. Furuuchi;Y. Kawai;Yuhei Yamamoto;T. Sugihara;T. Moriuchi
通讯作者：
A. Tsutsumida;J. Hamada;M. Tada;T. Aoyama;K. Furuuchi;Y. Kawai;Yuhei Yamamoto;T. Sugihara;T. Moriuchi

HOX genes as cancer-related genes in lung cancer.

HOX基因作为肺癌中的癌症相关基因。