High expression of the CKIP-1 gene might promote apoptosis through downregulation of the Ras/ERK signalling pathway in the intestinal type of gastric cancer.

Abstract

ObjectiveTo investigate the effect of the casein kinase 2 interacting protein 1 (CKIP-1) on the apoptosis of the intestinal type of gastric cancer (GC).MethodsThe levels of CKIP-1 protein and the rates of apoptosis were measured in tissue samples of the intestinal type of GC and human GC cell lines. The rate of apoptosis and the protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate specific protease 3 (cleaved caspase-3), cleaved caspase-9, rat sarcoma (Ras), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were analysed in SGC7901 cells expressing CKIP-1 short hairpin RNA (shRNA; knockdown) and SGC7901 cells overexpressing CKIP-1.ResultsThe levels of CKIP-1 protein were significantly lower in the intestinal type of GC tissues compared with the samples of intestinal metaplasia. Both the levels of CKIP-1 protein and the levels of apoptosis decreased gradually with decreasing cell differentiation in the intestinal type of GC tissue and cell lines; and they were positively correlated. In the CKIP-1 shRNA group, the rate of apoptosis and the levels of Bax, cleaved caspase-3 and cleaved caspase-9 were decreased; and the levels of Bcl-2, Ras and the ratio of p-ERK/ERK were increased, compared with the control group. Opposite results were observed in the CKIP-1 overexpression group.ConclusionHigh levels of CKIP-1 protein may promote apoptosis in the intestinal type of GC, possibly via the downregulation of the Ras/ERK signalling pathway.