Is gap junction the defensive factor against development, progression, and metastasis of gastric cancer?

间隙连接是胃癌发生、进展和转移的防御因子吗？

• 批准号: 13670491
• 负责人: MINE Tetsuya
• 金额: $ 0.7万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670491/
• 关键词: Gap junction; Intercellular communication; Cultured gastric cancer cells; Cultured gastric mucosal cells; Wnt signaling; WNT8B; FRAT2; Connexin; lucifer yellow; dye transfer

The role of gap junction in development ,progression and metastasis of gastric cancer was investigated in this project. First, gap junction formation was confirmed to be made during the culture and differentiation of gastric mucosal cells originated from rabbit fetus. Next, the expression of gap junction in the gastric cancer cell lines was examined and there was no expression during the culture and proliferation of the gastric cancer cell lines. To investigate the mechanism of progression and invasion of gastric cancer to the normal tissues, the expression of gap junction as well as proliferation was investigated using the coculture of normal gastric mucosal cells and gastric cancer cells. There was seen a gap junction between two cells and the proliferation activity of gastric cancer cells was decreased. At that time, it was considered that this project can be finished. Therefore, next, it was investigated how the expression of gap junction was regulated. Furthermore, it was confirmed that Wnt signaling including WNT8B and WNT10B was increased during the culture of gastric cancer cells. It seems that there is a reciprocal change between Wnt signaling and the expression of gap junction. Also, FRAT2, a mediator of Wnt signaling, was increased in parallel with proliferation of gastric cancer cells. From these data, it seems that the expression of gap junction might be regulated by Wnt signaling.

本研究旨在探讨缝隙连接在胃癌发生、发展和转移中的作用。首先，证实了兔胎胃粘膜细胞在培养和分化过程中形成了缝隙连接。接下来，检测了缝隙连接基因在胃癌细胞系中的表达，发现在胃癌细胞系的培养和增殖过程中没有表达。为探讨胃癌对正常组织的侵袭和进展机制，采用正常胃粘膜细胞与胃癌细胞共培养的方法，研究了细胞间隙连接的表达及细胞的增殖情况。两细胞间出现缝隙连接，胃癌细胞增殖活性降低。当时认为这个项目是可以完成的。因此，接下来，我们研究了缝隙连接的表达是如何调控的。进一步证实，在胃癌细胞培养过程中，包括WNT8B和WNT10B在内的Wnt信号增强。Wnt信号与缝隙连接的表达之间似乎存在着相互作用的变化。此外，Wnt信号的介导物FRAT2与胃癌细胞的增殖平行增加。从这些数据来看，缝隙连接的表达可能受Wnt信号的调控。

项目成果

Imai K et al.: "Zonal difference in inhibition of DNA synthesis caused by anesthetics in cultured rat hepatocytes"Jap J Anesth. 51. 505-508 (2002)

Imai K 等人：“培养大鼠肝细胞中麻醉剂引起的 DNA 合成抑制的区域差异”Jap J Anesth。

Saitoh T: "Proto-oncogenic WNT 10β is up-regulated by tumor necrosis α in human gastric cancer cell line MKN45"Inter J Oncol. 19. 1187-1192 (2001)

Saitoh T：“在人胃癌细胞系 MKN45 中，原癌性 WNT 10β 被肿瘤坏死 α 上调”Inter J Oncol. 19. 1187-1192 (2001)

Saitoh T et al: "Expression and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines: up-regulation of WNT8B mRNA by beta-estradiol in MCF-7 cells, and down-regulation of WNT8A and WNT8B mRNAs by retinoic acid in NT2 cells"Int J Oncol. 20. 999-10

Saitoh T 等人：“人类肿瘤细胞系中 WNT8A 和 WNT8B mRNA 的表达和调节：MCF-7 细胞中 β-雌二醇上调 WNT8B mRNA，NT2 细胞中视黄酸下调 WNT8A 和 WNT8B mRNA

Nagata J et al.: "Angiopoietin-1 and vascular endothelial growth factor expression in human esophageal cancer"Int J Mol Med. 10. 423-426 (2002)

Nagata J 等：“Angiopoietin-1 和血管内皮生长因子在人食管癌中的表达”Int J Mol Med。

Nagata J et al: "Angiopojetin-1 and vascular endothelial growth factor expression in human esophageal cancer"Int J Mol Med. 10. 423-426 (2002)

Nagata J 等人：“Angiopojetin-1 和血管内皮生长因子在人食管癌中的表达”Int J Mol Med。