Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells

Liu,Geng; Liu,Yuan-Jie; Lian,Wen-Jing; Zhao,Zhi-Wei; Yi,Tao; Zhou,Hong-Ying

doi:10.3892/or.2014.3224

Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells

Authors:
- Geng Liu
- Yuan-Jie Liu
- Wen-Jing Lian
- Zhi-Wei Zhao
- Tao Yi
- Hong-Ying Zhou
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Affiliations: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China, 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
Published online on: May 29, 2014 https://doi.org/10.3892/or.2014.3224
Pages: 581-588

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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.

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