title: Down-regulation of BRMS1 by DNA hypermethylation and its association with metastatic progression in triple-negative breast cancer.
abstract: Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in several solid tumors. However, the expression and function of BRMS1 in triple-negative breast cancer (TNBC) have not been reported. In this study, we found that BRMS1 was down-regulation in breast cancer cell lines and primary TNBC, while decreased expression of BRMS1 mRNA was significantly associated with lymph node metastasis. And this down-regulation was found to be in accordance with aberrant methylation of the gene. Hypermethylation of the gene was observed in 53.4% (62/116) of the TNBC primary breast carcinomas, while it was found in only 24.1% (28/116) of the corresponding nonmalignant tissues. In addition, BRMS1 expression was restored in MDA-MB-231 after treatment with the demethylating agent, 5-aza-2-deoxycytidine (5-Aza-dC), and demethylation of the highly metastatic cells MDA-MB-231 induced invasion suppression of the cells. Furthermore, the suppression of BRMS1 by siRNA transfection enhanced cancer cells invasion. Collectively, our results suggest that the aberrant methylation of BRMS1 frequently occurs in the down-regulation of BRMS1 in TNBC and that it may play a role in the metastasis of breast cancer.
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cerebrovascular Disease Research Institute, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Jin
authors.affiliation: Department of Medical Administration, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University Qingdao 266003, P. R. China.
authors.forename: Zhao-Chuan
authors.initials: ZC
authors.lastname: Yang
mesh_terms: D000328:Adult; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D018450:Disease Progression; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C410024:BRMS1 protein, human; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012097:Repressor Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: Triple-negative breast cancer; breast cancer metastasis suppressor 1; metastasis; methylation