The role of InsP3 receptor expression in gastric cancer patients

肌醇1,4,5-三磷酸受体（InsP3R）介导上皮内Ca2+信号传导并调节细胞功能，如分泌、凋亡和细胞增殖。一种或多种InsP3R异构体的缺失与诸如胆汁淤积等疾病过程有关。在这里，我们研究了InsP3R异构体的表达是否也可能与疾病的发展有关。在40例手术切除的胃癌组织中评估了所有三种InsP3R亚型的表达。在正常结肠黏膜和结直肠癌中均可见到InsP3Rs的所有亚型。结直肠粘膜可见密集的InsP3受体根尖定位。同时，在结直肠癌中可见到InsP3受体的弥漫性表达。胃癌患者IP3受体表达与临床参数无相关性。shRNA敲低CACO-2结肠癌细胞III型InsP3R可促进细胞凋亡，而过表达该受体可抑制细胞凋亡。因此，III型InsP3R在人类癌症中开始表达，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作用。这些发现表明，Ca2+信号通过这种InsP3R异构体在人类癌症中起着以前未被认识到的作用。

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.