PMID- 25071010 OWN - NLM STAT- MEDLINE DCOM- 20150603 LR - 20220321 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 5 IP - 16 DP - 2014 Aug 30 TI - Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer. PG - 6909-22 AB - 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 DeltaNp73 in MCF-7 cell line, knockdown of Nrf-2 gene resulted in an abrogation of TAp73 and DeltaNp73 expression in the cells transfected with sh-Nrf-2 as well as Nrf-2 knock out mouse model. However, we found Nrf-2 induced DeltaNp73 expression was abolished with 5-aza-dC treatment, thus lead to a down-regulated DeltaNp73 and an up-regulated TAp73 expression in breast cancer cells lines. Consistent with this model, we detected decreased TAp73 and increased DeltaNp73 expression in breast cancer tissue, along with increased TAp73 but decreased DeltaNp73 expression in corresponding surrounding noncancerous tissues (NCTs) in a breast cancer tissue assay. A significant inverse correlation was found between TAp73 and DeltaNp73 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 DeltaNp73 expression plays a critical role in breast cancer development. FAU - Lai, Jing AU - Lai J AD - Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China; These authors contributed equally to this work. FAU - Nie, Weiwei AU - Nie W AD - Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China; These authors contributed equally to this work. FAU - Zhang, Wenwen AU - Zhang W AD - Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; These authors contributed equally to this work. FAU - Wang, Yucai AU - Wang Y AD - Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. FAU - Xie, Ruilian AU - Xie R AD - Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China. FAU - Wang, Yanru AU - Wang Y AD - Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China. FAU - Gu, Jun AU - Gu J AD - Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Xu, Jing AU - Xu J AD - Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Song, Wei AU - Song W AD - Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China. FAU - Yang, Fang AU - Yang F AD - Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Huang, Guichun AU - Huang G AD - Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Cao, Peng AU - Cao P AD - Laboratory of Cellular and Molecular Biology, Jiangsu Province Institute of Chinese Medicine, Nanjing, China. FAU - Guan, Xiaoxiang AU - Guan X AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (DNA-Binding Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Nuclear Proteins) RN - 0 (TP73 protein, human) RN - 0 (Trp73 protein, mouse) RN - 0 (Tumor Protein p73) RN - 0 (Tumor Suppressor Proteins) RN - 0 (delta Np73 protein, human) SB - IM MH - Animals MH - Apoptosis/genetics MH - Breast Neoplasms/*genetics/pathology MH - Cell Proliferation/genetics MH - *CpG Islands MH - *DNA Methylation MH - DNA-Binding Proteins/*genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Genes, Tumor Suppressor MH - Humans MH - MCF-7 Cells MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - NF-E2-Related Factor 2/*genetics MH - Nuclear Proteins/*genetics MH - Promoter Regions, Genetic MH - Transfection MH - Tumor Protein p73 MH - Tumor Suppressor Proteins/*genetics PMC - PMC4196172 COIS- Conflict of Interest The authors declare that they have no competing interests. EDAT- 2014/07/30 06:00 MHDA- 2015/06/04 06:00 PMCR- 2014/08/01 CRDT- 2014/07/30 06:00 PHST- 2014/07/30 06:00 [entrez] PHST- 2014/07/30 06:00 [pubmed] PHST- 2015/06/04 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 2230 [pii] AID - 10.18632/oncotarget.2230 [doi] PST - ppublish SO - Oncotarget. 2014 Aug 30;5(16):6909-22. doi: 10.18632/oncotarget.2230.