Stomach-specific c-Myc overexpression drives gastric adenoma in mice through AKT/mammalian target of rapamycin signaling

Jing Liu; Wenxin Feng; Min Liu; Hanyu Rao; Xiaoxue Li; Yan Teng; Xiao Yang; Jin Xu; Weiqiang Gao; Li Li

doi:10.17305/bjbms.2020.4978

Authors

Jing Liu State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China https://orcid.org/0000-0002-1273-3119
Wenxin Feng State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
Min Liu State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
Hanyu Rao State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China https://orcid.org/0000-0003-1286-8707
Xiaoxue Li State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
Yan Teng State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China
Xiao Yang State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China https://orcid.org/0000-0002-0298-9831
Jin Xu School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
Weiqiang Gao State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
Li Li State Key Laboratory of Oncogenes and Related Genes, Renji Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China https://orcid.org/0000-0003-2342-3658

DOI:

https://doi.org/10.17305/bjbms.2020.4978

Keywords:

c-Myc, gastric adenoma, transgenic, AKT/mammalian target of rapamycin

Abstract

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 transgenic mouse model to investigate its role in GC. We found that overexpression of c-Myc in Atp4b⁺ gastric parietal cells could induce gastric adenoma 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 tumorigenesis can be induced by c-Myc overexpression through activation of the AKT/mTOR pathway.