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Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis

Published on Jan 1, 2016in Cancer Research8.38
· DOI :10.1158/0008-5472.CAN-15-0692
Larysa V. Yuzefovych7
Estimated H-index: 7
(USA: University of South Alabama),
Andrea G. Kahn5
Estimated H-index: 5
(USA: University of South Alabama)
+ 5 AuthorsLyudmila I. Rachek13
Estimated H-index: 13
(USA: University of South Alabama)
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 1alpha in mitochondria (Tg), and mice simultaneously lacking OGG1 and overexpressing human OGG1 subunit 1alpha 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
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References20
Newest
#1Jorming Goh (UW: University of Washington)H-Index: 8
#2Linda C. Enns (UW: University of Washington)H-Index: 14
Last.Warren Ladiges (UW: University of Washington)H-Index: 27
view all 7 authors...
#1J. Kim (USA: University of South Alabama)H-Index: 1
#2Min Xu (USA: University of South Alabama)H-Index: 3
Last.Valentina Grishko (USA: University of South Alabama)H-Index: 19
view all 7 authors...
#1Kaori Ishikawa (University of Tsukuba)H-Index: 12
#2Keizo Takenaga (Shimane University)H-Index: 28
Last.Jun-Ichi Hayashi (University of Tsukuba)H-Index: 40
view all 9 authors...
Cited By13
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#1Lei Zhang (CSU: Central South University)H-Index: 60
#2Yiyi Liang (CSU: Central South University)H-Index: 1
Last.Fenglei Yu (CSU: Central South University)H-Index: 1
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#1Karen M. Bussard (Thomas Jefferson University)H-Index: 12
#2Linda D. Siracusa (Thomas Jefferson University)H-Index: 33
#1Timothy C. Kenny (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 3
#2Peter C. Hart (UIC: University of Illinois at Chicago)H-Index: 6
Last.Doris Germain (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 20
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#1Linlin Zhang (Fudan University Shanghai Medical College)H-Index: 1
#2Aurelio Reyes (University of Cambridge)H-Index: 34
Last.Xiangdong Wang (Fudan University Shanghai Medical College)H-Index: 1
view all 3 authors...
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