Expression and Alternative Splicing Variant of Gastrin / Cholecystokinin Type B Receptor in Gastric Cancer

Hwang, You Jin; Yoo, Jong Hyun; Choi, Deok Ju; Park, Jong Jae; Kim, Sun Suk; Oh, Jae Hwan; Lee, Woon Ki; Kang, Dong Hoon

Abstract

BACKGROUND/AIMS: Gastrin exert a variety of biologic actions in the brain and gastrointestinal tract through cholecystokinin receptors. Gastrin/cholecystokinin type B receptor (CCK-BR) mRNA has been shown in some colorectal cell lines and gastrointestinal tumors. While human CCK-BR has been characterized, the relative role of their isoforms in gastrointestinal cancer remains unclear. We investigated expression of CCK-BR and its isoform in normal and malignant tissues obtained from patients with gastric cancer according to anatomic location of the primary lesion, histologic type, and extent of disease.
METHODS
RT-PCR was used to evaluate mRNA expression of CCK-BR and its isoforms in cancer and normal samples obtained from 44 patients with gastric adenocarcinoma. The expression of long-type isoform transcripts of CCK-BR was evaluated by Southern blot analysis.
RESULTS
CCK-BR was expressed in 33/44 (75%) of malignant tissues and 36/39 (92.3%) of normal tissues obtained from the patients. By AJCC classification, CCK-BR transcript was detected in 33.3% of patients in IA stage, 50% of IB, 54.5% of II, 81.8% of IIIA, and 100% of both IIIB and IV. Long-type isoform transcript of CCK-BR was detected in 14/30 (46.7%) of malignant tissues and 23/31 (74.2%) of normal tissues of patients with gastric cancer.
CONCLUSION
In conclusion, the expression of CCK-BR indicates tumor grade and presence of metastatic disease, and loss of long isoform transcript of CCK-BR may be related with the processing of gastric cancer.