title: Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer.
abstract: To understand the transcriptional regulation of p73 by promoter methylation and Nrf-2 in breast carcinogenesis, ChIP assay indicated that Nrf-2 can bind to both promoters and can activate the transcription of TAp73 and ΔNp73 in MCF-7 cell line, knockdown of Nrf-2 gene resulted in an abrogation of TAp73 and ΔNp73 expression in the cells transfected with sh-Nrf-2 as well as Nrf-2 knock out mouse model. However, we found Nrf-2 induced ΔNp73 expression was abolished with 5-aza-dC treatment, thus lead to a down-regulated ΔNp73 and an up-regulated TAp73 expression in breast cancer cells lines. Consistent with this model, we detected decreased TAp73 and increased ΔNp73 expression in breast cancer tissue, along with increased TAp73 but decreased ΔNp73 expression in corresponding surrounding noncancerous tissues (NCTs) in a breast cancer tissue assay. A significant inverse correlation was found between TAp73 and ΔNp73 expression in the above tissue-array (P = 0.047) and validated in another set consisting of 128 breast cancer tumor tissue (P = 0.034). Taken together, our findings suggest that Nrf-2 and promoter methylation cooperatively govern the transcriptional regulation of p73, and unbalanced expression of TAp73 and ΔNp73 expression plays a critical role in breast cancer development.
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China; These authors contributed equally to this work.
authors: Jing
authors: J
authors: Lai
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China; These authors contributed equally to this work.
authors: Weiwei
authors: W
authors: Nie
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; These authors contributed equally to this work.
authors: Wenwen
authors: W
authors: Zhang
authors: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
authors: Yucai
authors: Y
authors: Wang
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China.
authors: Ruilian
authors: R
authors: Xie
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China.
authors: Yanru
authors: Y
authors: Wang
authors: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Jun
authors: J
authors: Gu
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Jing
authors: J
authors: Xu
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China.
authors: Wei
authors: W
authors: Song
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Fang
authors: F
authors: Yang
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Guichun
authors: G
authors: Huang
authors: Laboratory of Cellular and Molecular Biology, Jiangsu Province Institute of Chinese Medicine, Nanjing, China.
authors: Peng
authors: P
authors: Cao
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China; Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Xiaoxiang
authors: X
authors: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009687:Nuclear Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human