Esophageal 3D organoids of MPV17^-/- mouse model of mitochondrial DNA depletion show epithelial cell plasticity and telomere attrition.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with late-stage detection and poor prognosis. This emphasizes the need to identify new markers for early diagnosis and treatment. Altered mitochondrial genome (mtDNA) content in primary tumors correlates with poor patient prognosis. Here we used three-dimensional (3D) organoids of esophageal epithelial cells (EECs) from the MPV17^-/- mouse model of mtDNA depletion to investigate the contribution of reduced mtDNA content in ESCC oncogenicity. To test if mtDNA defects are a contributing factor in ESCC, we used oncogenic stimuli such as ESCC carcinogen 4-nitroquinoline oxide (4-NQO) treatment, or expressing p53^R175H oncogenic driver mutation. We observed that EECs and 3D-organoids with mtDNA depletio

SUBMITTER: Guha M 

PROVIDER: S-EPMC6817447 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature