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Correction: Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis
- Source :
- Cancer research. 81(11)
- Publication Year :
- 2021
-
Abstract
- Production of mitochondrial reactive oxygen species and integrity of mitochondrial DNA (mtDNA) are crucial in breast cancer progression and metastasis. Therefore, we evaluated the role of mtDNA damage in breast cancer by genetically modulating the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the PyMT transgenic mouse model of mammary tumorigenesis. We generated mice lacking OGG1 (KO), mice overexpressing human OGG1 subunit 1α in mitochondria (Tg), and mice simultaneously lacking OGG1 and overexpressing human OGG1 subunit 1α in mitochondria (KO/Tg). We found that Tg and KO/Tg mice developed significantly smaller tumors than KO and wildtype mice after 16 weeks. Histological analysis revealed a roughly two-fold decrease in the incidence of lung metastases in Tg mice (33.3%) compared to wildtype mice (62.5%). Furthermore, lungs from Tg mice exhibited nearly a 15-fold decrease in the average number of metastatic foci compared to WT mice (p≤0.05). Primary tumors isolated from Tg mice also demonstrated reduced total and mitochondrial oxidative stress, diminished mtDNA damage, and increased mitochondrial function. Targeting hOGG1 to the mitochondria protected cells from mtDNA damage resulting in downregulation of HIF-1α and attenuated phosphorylation of Akt. Collectively, we demonstrate proof of concept that mtDNA damage results in breast cancer progression and metastasis in vivo. Moreover, our findings offer new therapeutic strategies for modulating the levels of mtDNA repair enzymes to delay or stall metastatic progression.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.diagnostic_test
Biology
medicine.disease
Article
Metastasis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Breast cancer
Oncology
Western blot
Mitochondrial DNA repair
030220 oncology & carcinogenesis
medicine
Cancer research
Southern blot
Subjects
Details
- ISSN :
- 15387445
- Volume :
- 81
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....7062cf347a8690694c076556387c6a55