Arsenic exposure increases susceptibility to Ptpn11-induced malignancy in mouse embryonic fibroblasts through mitochondrial hypermetabolism.

ABSTRACT:

Objective

To explore the synergistic effect and metabolic mechanism of chronic arsenic exposure and PTPN11 gain-of-function mutation on tumorigenesis.

Methods

Arsenic-transformed Ptpn11^+/+ (WT-As) and Ptpn11^D61G/+ -mutant (D61G-As) mouse embryonic fibroblasts (MEFs) were established by chronic treatment of low-dose arsenic. We used cell counting, plate colony and soft agar colony formation, and a nude mouse xenograft model to detect malignant transformation and tumorigenesis in vitro and in vivo. To detect mitochondrial oxidative phosphorylation (OXPHOS), we used Seahorse real-time cell metabolic analysis as well as adenosine triphosphate (ATP) and ROS production assays. Lastly, we examined mTOR signaling pathway chang

SUBMITTER: Yang F 

PROVIDER: S-EPMC9360862 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature