Increased Proliferation Of Human Gastricarcinoma Cell Line Bgc823 Transfected With Midkine And Truncated Midkine Gene

Midkine (MK) regulates cell growth, survival and differentiation, and increased MK expression is frequently detected in various types of human carcinomas. In association with MK, a truncated form of MK (tMK) mRNA that encodes an MK lacking the N-terminal domain, has been not detected in adjacent normal tissues, but in many cancer tissues. However, it remains unclear whether MK and tMk gene transfection can contribute to gastric tumorigenesis. In the present study, we investigate the impact of the increased MK and tMK expressions on cell growth of BGC823 (gastric gland carcinoma cell line) and tumor formation in nude mice. The results showed that the growth of MK and tMK transfectant cells was significantly promoted compared the parent BGC823 and vector transfectant cells, and tMK transfectant cells grew more rapidly than MK transfectant cells. The numbers of colony formation of the cells transfected MK or tMk gene were more than those of control cells. In nude mice, visible tumor was observed earlier in MK transfectant cells-and tMK transfectant cells-injected mice than the parent BGC823-and vector transfectant cells-injected mice, and the tumor grew bigger and more weight in MK transfectant cells-and tMK transfectant cells-injected mice than in control mice. These results suggest that overexpressed MK or tMK can promte human gastric cancer cell growth in vitro and tumorigenesis in vivo, and tMK gene transfection possess stronger effect than MK. The tMK may be a more promising gene therapeutic target compared with MK for the treatment of malignant tumors.