Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway.

Regenerating gene family member 4 (REG4), a secreted protein, is overexpressed in several cancers, including gastric cancer. The present study was undertaken to determine the roles of REG4 in the growth of gastric cancer in the nude mice and in the proliferation and migration in human gastric cancer cell line and its downstream signaling pathway. Gastric cancer models were elicited by intraperitoneally injecting MKN45 human gastric cancer cells and the tumor size was measured every other day. The expressions of REG4 mRNA and protein were increased in the gastric cancer tissues from gastric cancer patients. REG4 increased the gastric tumor weight and size in the nude mice, and promoted the proliferation and migration of gastric cancer cells MKN45. Adeno-associated viral (AAV)-mediated knockdown of REG4 decreased the gastric tumor weight and size in the nude mice, and suppressed the proliferation and migration of MKN45 cells. REG4 increased the expression of phosphorylated protein kinase B (Akt). Triciribine hydrate (TCN), the inhibitor of Akt, decreased the gastric tumor weight and size in the nude mice and abolished REG4-induced weight and size increase of the tumor. TCN also inhibited proliferation and migration and abolished REG4-induced proliferation and migration increase of human gastric cell line MKN45. These results indicate that REG4 promotes the growth, proliferation and migration of gastric cancer through Akt pathway.