胃特异性 c-Myc 过表达通过 AKT/雷帕霉素靶蛋白信号通路驱动小鼠胃腺瘤的发生。

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

机构信息

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.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China.

出版信息

Bosn J Basic Med Sci. 2021 Aug 1;21(4):434-446. doi: 10.17305/bjbms.2020.4978.

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.

胃癌（GC）是世界上最常见的恶性癌症之一。c-Myc 是一种众所周知的癌基因，在许多癌症中都普遍扩增，包括胃癌。然而，c-Myc 在 GC 中的作用仍不完全清楚。在这里，我们生成了一种胃特异性 c-Myc 转基因小鼠模型，以研究其在 GC 中的作用。我们发现，c-Myc 在 Atp4b+胃壁细胞中的过表达可诱导小鼠发生胃腺瘤。在机制上，c-Myc 通过 AKT/mTOR 通路促进肿瘤发生。此外，AKT 抑制剂（MK-2206）或 mTOR 抑制剂（雷帕霉素）抑制 c-Myc 过表达的胃癌细胞系的增殖。因此，我们的研究结果表明，通过激活 AKT/mTOR 通路，c-Myc 的过表达可诱导胃肿瘤发生。