title: BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells.
abstract: BACKGROUND
  The role of B Lymphocyte Stimulator (BLyS) in the survival of malignant B cells and the maintenance of normal B cell development and homeostasis has been intensively studied in the literature. However, the influence of BLyS on breast cancer progression remains unclear. The study aimed to investigate the effect of hypoxia on BLyS regulation, cell migratory response to BLyS and the possible molecular mechanisms.
  
  
  METHODS
  In this study, we examined the role of BLyS in the migration of human breast cancer cells by transwell assay. We also explored whether BLyS and its receptors expressed in human breast cancer cell lines by immunofluorescence and Western Blotting. Then we detected the expression level of BLyS in both normoxic and hypoxic conditions by real time-PCR and Western Blotting. Pathways involved were confirmed by Western Blotting, immunofluorescence, transwell assay and luciferase assay.
  
  
  RESULTS
  According to our study, the expression level of BlyS was increased in human breast cancer cell lines in hypoxic conditions. Up-regulation of this protein led to activation and nuclear translocation of NF-kappa B p65. We also found that the number of migrated cells was increased in the presence of BLyS and inhibition of phosphorylation of Akt attenuated the enhanced migratory response.
  
  
  CONCLUSIONS
  It suggested that better understanding of BLyS, an immunopotentiator, may offer a potential therapeutic target for the treatment of human breast cancers. In addition, BLyS promoted breast cancer cells migration, underscoring the necessity of appropriate applications of immunopotentiators to cancer treatment.
authors.affiliation: National Nanjing New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, Peoples Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
authors.forename: Renping
authors.initials: R
authors.lastname: Zhao
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhou
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fang
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Wenting
authors.initials: W
authors.lastname: Shi
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics* / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; D051996:Transcription Factor RelA; D053303:Transmembrane Activator and CAML Interactor Protein; D051057:Proto-Oncogene Proteins c-akt