The role of InsP3 receptor expression in gastric cancer patients

InsP3受体表达在胃癌患者中的作用

• 批准号: 20591583
• 负责人: SHIBAO Kazunori
• 金额: $ 2.91万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591583/
• 关键词: カルシウムシグナリング; IP3レセプター; 胃癌; 細胞増殖; アポトーシス; イノシトール3リン酸受容体

The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca2+ signaling in epithelia and regulates cellular functions such as secretion, apoptosis and cell proliferation. Loss of one or more InsP3R isoform has been implicated in disease processes such as cholestasis. Here we examined whether gain of expression of InsP3R isoforms also may be associated with development of disease. Expression of all three InsP3R isoforms was evaluated in tissue from gastric carcinomas surgically resected from 40 patients. All subtypes of InsP3Rs were seen in both normal colorectal mucosa and colorectal cancer. Dense apical localization of InsP3 receptors were seen in colorectal mucosa. Meanwhile, diffuse expression of InsP3 receptors were seen in colorectal cancer. No correlation between IP3 receptor expression and clinical parameter were observed in gastric cancer patients. shRNA knockdown of type III InsP3R in CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in human cancer, and its expression level is directly related to aggressiveness of the tumor, which may reflect inhibition of apoptosis by the receptor. These findings suggest a previously unrecognized role for Ca2+ signaling via this InsP3R isoform in human cancer.

1，4，5-三磷酸肌醇受体（InsP 3R）介导上皮细胞中的Ca 2+信号并调节细胞功能，如分泌、凋亡和细胞增殖。一个或多个InsP 3R同种型的缺失与疾病过程如胆汁淤积有关。在这里，我们研究了InsP 3R亚型表达的增加是否也可能与疾病的发展有关。所有三个InsP 3R亚型的表达进行了评估，从40例胃癌手术切除的组织。InsP 3R的所有亚型在正常结直肠粘膜和结直肠癌中均可见。InsP 3受体在结直肠粘膜中可见密集的顶端定位。InsP 3受体在大肠癌中呈弥漫性表达。胃癌患者IP 3受体表达与临床参数无相关性。在CACO-2结肠癌细胞中，III型InsP 3R的shRNA敲低增强了凋亡，而受体的过表达降低了凋亡。因此，III型InsP 3R在人类癌症中表达，其表达水平与肿瘤的侵袭性直接相关，这可能反映了受体对细胞凋亡的抑制。这些发现表明，以前未被认识到的作用，钙信号通过这种InsP 3R亚型在人类癌症。

项目成果

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The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma.

• DOI: 10.1016/j.ceca.2010.09.005
• 发表时间: 2010-12
• 期刊: Cell calcium
• 影响因子: 4
• 作者: Shibao K;Fiedler MJ;Nagata J;Minagawa N;Hirata K;Nakayama Y;Iwakiri Y;Nathanson MH;Yamaguchi K
• 通讯作者: Yamaguchi K