The role of InsP3 receptor expression in gastric cancer patients

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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.