title: Expression of breast cancer metastasis suppressor-1, BRMS-1, in human breast cancer and the biological impact of BRMS-1 on the migration of breast cancer cells.
abstract: Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers.
  
  
  METHODS
  BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Human breast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored.
  
  
  RESULTS
  BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (p<0.05). Blocking phospholipase-Cγ (PLCγ) had a significant influence on the BRMS-1-induced cell migration. Finally, significantly low levels of BRMS1 were observed in patients with high-grade tumors (p=0.12), in patients with distant metastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035).
  
  
  CONCLUSIONS
  BRMS-1 is aberrantly expressed in human breast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.
authors.affiliation: Metastasis and Angiogenesis Research Group, CUPUCI, Cardiff University School of Medicine, Henry Welcome Building, Heath Park, Cardiff CF14 4XN, U.K. JiangW@cardiff.ac.uk.
authors.forename: Yulu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Tan
authors.forename: Pinghui
authors.initials: P
authors.lastname: Sun
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins
keywords: BRMS-1; PLC-γ; breast cancer; cell migration; metastasis; survival