title: Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis.
abstract: Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients' in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients' clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.
authors.affiliation: Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt.
authors.forename: Mona M
authors.initials: MM
authors.lastname: Mohamed
authors.affiliation: Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt.
authors.forename: Salwa
authors.initials: S
authors.lastname: Sabet
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Dun-Fa
authors.initials: DF
authors.lastname: Peng
authors.affiliation: Department of Pathology, National Cancer Institute, Cairo University, Giza 12613, Egypt.
authors.forename: M Akram
authors.initials: MA
authors.lastname: Nouh
authors.affiliation: Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
authors.forename: Mohamed
authors.identifier: 0000-0003-3645-2343
authors.initials: M
authors.lastname: El-Shinawi
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
mesh_terms: D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D005979:Glutathione Peroxidase