Downregulated expression of CIAPIN1 may contribute to gastric carcinogenesis by accelerating cell proliferation and promoting cell cycle progression

Abstract

Our previous studies revealed that cytokine induced apoptosis inhibitor 1 (CIAPIN1), which was reported to be essential in mouse definitive hematopoiesis, was related to multidrug resistance in gastric cancer cells and that the distribution of CIAPIN1 in normal human tissues was similar to the distribution of Ras. This study aimed to explore whether CIAPIN1 plays a role in gastric carcinogenesis. Expression of CIAPIN1 in normal, inflammatory gastric mucosa, gastric precancerous lesions and gastric adenocarcinoma was detected by immunohistochemistry and western blotting and, influence of CIAPIN1 on the proliferation of gastric cancer cells was investigated by ectopic expression of CIAPIN1 and RNA interference (RNAi). Our immunohistochemical results demonstrated that the expression of CIAPIN1 in gastric antral mucosa was progressively reduced along the sequence of normal/inflammatory gastric mucosa-atrophy-intestinal metaplasia-dysplasia-adenocarcinoma. The downregulation of CIAPIN1 in cancerous tissues was further confirmed by western blotting. No relationship between the expression level of CIAPIN1 and the clinicopathological parameters such as age, gender, differentiation, TNM stage and the existence of metastasis was found in gastric cancer patients. In in vitro cellular experiments, ectopic expression of CIAPIN1 by cDNA transfection resulted in suppression of cell proliferation and inhibition of cell cycle progression while knockdown of CIAPIN1 with siRNA accelerated cell proliferation and promoted cell cycle progression in SGC7901 and MKN28 gastric cancer cells. These results suggest that downregulated CIAPIN1 expression may contribute to gastric carcinogenesis by accelerating cell proliferation and promoting cell cycle progression. ©2009 Landes Bioscience.