Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin. Free Radic Res 2017 Jun;51(6):582-590
Date
06/08/2017Pubmed ID
28587495Pubmed Central ID
PMC5683088DOI
10.1080/10715762.2017.1339303Scopus ID
2-s2.0-85021841587 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Manganese superoxide dismutase (MnSOD) is a mitochondrial-resident enzyme that reduces superoxide to hydrogen peroxide (H2O2), which can be further reduced to water by glutathione peroxidase (GPX1). Data from human studies have indicated that common polymorphisms in both of these proteins are associated with the risk of several cancers, including breast cancer. Moreover, polymorphisms in MnSOD and GPX1 were shown to interact to increase the risk of breast cancer. To gain an understanding of the molecular mechanisms behind these observations, we engineered human MCF-7 breast cancer cells to exclusively express GPX1 and/or MnSOD alleles and investigated the consequences on the expression of several proteins associated with cancer aetiology. Little or no effect was observed on the ectopic expression of these genes on the phosphorylation of Akt, although allele-specific effects and interactions were observed for the impact on the levels of Bcl-2, E-cadherin and Sirt3. The patterns observed were not consistent with the steady-state levels of H2O2 determined in the transfected cells. These results indicate plausible contributing factors to the effects of allelic variations on cancer risk observed in human epidemiological studies.
Author List
Ekoue DN, Bera S, Ansong E, Hart PC, Zaichick S, Domann FE, Bonini MG, Diamond AMMESH terms used to index this publication - Major topics in bold
AllelesAntigens, CD
Cadherins
Cell Engineering
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic
Glutathione Peroxidase
Humans
Hydrogen Peroxide
MCF-7 Cells
Mitochondria
Phosphorylation
Plasmids
Polymorphism, Genetic
Protein Binding
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2
Signal Transduction
Sirtuin 3
Superoxide Dismutase
Transfection
