Ikeo Koichi, Oshima Tadayuki, Shan Jing, Matsui Hirofumi, Tomita Toshihiko, Fukui Hirokazu, Watari Jiro, Miwa Hiroto
Hepatogastroenterology. 2015 Mar-Apr;62(138):540-5.
BACKGROUND/AIMS: Junctional adhesion molecules (JAMs) are known as integral constituents of cellular tight junctions. However, the functions of JAMs in cancer tissues are controversial and the function of JAM-A in gastric cancer is unclear. Acordingly, we investigated the function of JAM-A in gastric epithelial and gastric cancer cell proliferation, invasion and apoptosis.
A normal rat gastric mucosa-derived cell line (RGM1), a rat gastric cancer-like cell line established from RGM1 (RGK1), and a human gastric cancer cell line (NCI-N87) were used in this study. To examine the expression of junctional proteins, immunoblotting and immunofluorescent staining were performed with specific antibodies (JAM-A, claudins, occludin and ZO-1). JAM-A was knocked down by small interfering RNA.
RGM1 and RGK1 expressed JAM-A, occludin and ZO-1 but not claudins. RGK1 were significantly more invasive than RGM1. JAM-A knock-down significantly decreased the proliferation and the invasion of RGK1 but not of RGM1. JAM-A knock-down significantly decreased the proliferation of NCI-N87 cells and significantly decreased expression of the anti-apoptotic protein Bcl-xL but not the expression of AKT or Mcl-1.
JAM-A promotes proliferation and inhibits apoptosis of gastric cancer, suggesting that it has a pivotal role in gastric cancer progression.
背景/目的：连接粘附分子（JAMs）是细胞紧密连接的重要组成部分。然而，JAMs在癌组织中的功能存在争议，且JAM-A在胃癌中的功能尚不清楚。因此，我们研究了JAM-A在胃上皮细胞和胃癌细胞增殖、侵袭及凋亡中的作用。
本研究使用了一种正常大鼠胃黏膜来源的细胞系（RGM1）、一种由RGM1建立的大鼠胃癌样细胞系（RGK1）以及一种人胃癌细胞系（NCI-N87）。为检测连接蛋白的表达，使用特异性抗体（JAM-A、闭合蛋白、闭锁蛋白和ZO-1）进行免疫印迹和免疫荧光染色。通过小干扰RNA敲低JAM-A。
RGM1和RGK1表达JAM-A、闭锁蛋白和ZO-1，但不表达闭合蛋白。RGK1的侵袭性明显高于RGM1。敲低JAM-A显著降低了RGK1的增殖和侵袭能力，但对RGM1没有影响。敲低JAM-A显著降低了NCI-N87细胞的增殖，并显著降低了抗凋亡蛋白Bcl-xL的表达，但对AKT或Mcl-1的表达没有影响。
JAM-A促进胃癌细胞增殖并抑制其凋亡，表明它在胃癌进展中起关键作用。
