title: Demethylation of Repressor Element-1 Silencing Transcription (REST) Suppresses the Malignant Phenotype of Breast Cancer via MMP9.
abstract: Breast cancer is the leading cause of cancer deaths in females all over the world, mainly resulting from metastasis. Previous studies have revealed that repressor element-1 (RE-1) silencing transcription (REST) acted as a tumor suppressor in breast cancer. However, the mechanism by which REST is regulated remains unknown, and its role in the metastasis in breast cancer cells remains unclear. In the present study, we showed that the expression of REST was lower in breast cancer samples than that of adjacent samples by immunohistochemical analysis, which may be due to hypermethylation of the REST promoter. Low REST levels are significantly associated with malignant progression in breast cancer patients. Additionally, we elucidated the functions of REST on proliferation and invasion in breast cancer cells. Lentivirus transfection was used to overexpress REST in human breast MDA-MB-231 cells. Then the biologic consequences of overexpressing REST in regard to cell proliferation, apoptosis, and invasion were determined. Furthermore, we also determined matrix metalloproteinase-9 (MMP9) as a target of REST. These results demonstrate that downregulation of REST, a tumor suppressor in breast cancer, is associated with hypermethylation. Induced REST expression is capable of attenuating invasion ability of breast cancer cells, which may be a novel strategy for metastatic breast cancer treatment.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Lv
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Jifang
authors.initials: J
authors.lastname: Wen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D014162:Transfection / Q000379:methods; D000099229:RE1-Silencing Transcription Factor
chemical_list: D020780:Matrix Metalloproteinase 9; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor