Stomach-specific c-Myc overexpression drives intestinal-type gastric cancer in mice via AKT/mTOR signaling

Gastric cancer (GC) is one of the most common malignant cancers in the world. c-Myc, a well-known oncogene, is commonly amplified in many cancers, including gastric cancer. However, it is still not completely understood how c-Myc functions in GC. Here, we generated a stomach-specific c-Myc knock-in mouse model to investigate its role in GC. We found that overexpression of c-Myc in Atp4b+ gastric parietal cells could induce intestinal-type gastric cancer in mice. Mechanistically, c-Myc promoted tumorigenesis via the AKT/mTOR pathway. Furthermore, AKT inhibitor (MK-2206) or mTOR inhibitor (Rapamycin) inhibited the proliferation of c-Myc overexpressing gastric cancer cell lines. Thus, our findings highlight that gastric cancer can be induced by c-Myc overexpression through activation of the AKT/mTOR pathway. Gastric mRNA profiles of 12-week old wild type (WT) and Atp4b-cre;MycOE mice were generated by deep sequencing, in triplicate.