Coexpression of cholecystokinin-B/gastrin receptor and gastrin gene in human gastric tissues and gastric cancer cell line

Abstract

AIM:To compare the expression patterns of cholecystokinin-B (CCK-B)/gastrin receptor genes in matched human gastric carcinoma and adjacent non-neoplastic mucosa of patients with gastric cancer, inflammatory gastric mucosa from patients with gastritis, normal stomachs from 2 autopsied patients and a gastric carcinoma cell line (SGC-7901), and to explore their relationship with progression to malignancy of human gastric carcinomas. METHODS:RT-PCR and sequencing were employed to detect the mRNA expression levels of CCK-B receptor and gastrin gene in specimens from 30 patients with gastric carcinoma and healthy bordering non-cancerous mucosa, 10 gastritis patients and normal stomachs from 2 autopsied patients as well as SGC-7901. The results were semi-quantified by normalizing it to the mRNA level of β-actin gene using Lab Image software. The sequences were analyzed by BLAST program. RESULTS:CCK-B receptor transcripts were detected in all of human gastric tissues in this study, including normal, inflammatory and malignant tissues and SGC-7901. However, the expression levels of CCK-B receptor in normal gastric tissues were higher than those in other groups (P<0.05), and its expressions did not correlate with the differentiation and metastasis of gastric cancer (P>0.05). On the other hand, gastrin mRNA was detected in SGC-7901 and in specimens obtained from gastric cancer patients (22/30) but not in other gastric tissues, and its expression was highly correlated with the metastases of gastric cancer (P<0.05).

Characterization of gastrins and their receptor in solid human gastric adenocarcinomas

“…Accordingly, long-term use of proton pump inhibitors has raised concerns about the ensuing hypergastrinemia [1][2][3], because hypergastrinemia increases the risk of gastric carcinogenesis in animal models [4,5]. Also cell line studies have implicated gastrin as a growth factor in gastric cancer cells [6][7][8][9][10][11][12].…”

Cholecystokinin and Gastrin Receptors

“…Expression of CCK2R in gastric cancer samples indicates that gastrin stimulates tumor growth by autocrine mechanisms (96,200,250,310,358,412,592). False-positive detection of CCK1R gene expression was also reported to correspond to sample contamination with noncancerous tissue (412).…”

Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor

“…Evidence of the permanent activation of CCK2R is rather scarce in the literature. A mis-spliced form of CCK2R retaining intron 4 (corresponding to an insertion of 69 amino acid residues in the middle of intracellular loop 3-ICL3, Figure A1) and expressed in stomach, colon, and pancreatic cancers [10,11,77] has been shown to be more effective compared to the wild type in mobilizing cytosolic calcium expressed in CHO cells [78]. The expression of this ICL3-expanded version of CCK2R in Balb3T3 cells was found to result in constitutive CCK2R activation and spontaneous calcium oscillations not blocked by the CCK2R antagonist CAM1028 [79], but such constitutive CCK2R activation and spontaneous calcium oscillations could not be confirmed after expression in CHO cells [78].…”

“…CCK2R is involved in anxiety and panic disorders and is correlated with suicidal behavior [2,[5][6][7]. In the periphery, CCK2R is expressed in gastrointestinal tissues [8][9][10][11]. Gastrin stimulation of CCK2R promotes gastric acid secretion [12], inhibits stomach emptying [13], inhibits colon motility [14], and in the long term promotes the branching morphogenesis of gastric epithelial cells [15].…”