title: Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells.
abstract: Bone morphogenetic protein 6 (BMP6) is an important regulator of cell growth, differentiation and apoptosis in various types of tumor. In breast cancer, it was considered as a tumor suppressor. Our previous study also confirmed that BMP6 was a critical regulator of breast cancer drug resistance. However, little is known about how its expression is regulated and its mechanisms in breast cancer drug resistance. In the present study, we assessed the DNA methylation regulation of BMP6 based on the presence of a large CpG island in the BMP6 gene promoter. Quantitative DNA methylation analyses showed a significantly increased DNA methylation level in the drug-resistant cell line MCF-7/ADR compared to their parental cells MCF-7. Moreover, the drug-resistant cell line MCF-7/ADR showed an EMT phenotype confirmed by morphology and the expression of EMT marker gene. MCF-7 cells transfected with BMP6-specific shRNA vector also showed an EMT phenotype. The MCF-7/ADR cells treated with the recombinant BMP6 proteins reversed their EMT phenotype. These data indicated that hypermethylation modifications contributed to the regulation of BMP6 and induced an EMT phenotype of breast cancer during the acquisition of drug resistance.
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Lian
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.affiliation: Biotherapy Laboratory of Gynecological Oncology, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of The Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Zhou
mesh_terms: D055418:Bone Morphogenetic Protein 6 / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6