title: Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen.
abstract: BACKGROUND
  BAG-1 (bcl-2 associated athanogene) is a multifunctional protein that protects cells from a wide range of apoptotic stimuli including radiation, hypoxia and chemotherapeutic agents. Overexpression of cytoplasmic BAG-1 has been associated with the increased survival and decreased response to treatment with tamoxifen (TAM) in breast cancer. We attempted to assess the expression of BAG-1 in the human breast cancer cells that are resistant to treatment with 4-OH TAM and effect of altered BAG-1 expression on their sensitivity to 4-OH TAM.
  
  
  METHODS
  BAG-1 expression was examined in the MCF-7 cells that became resistant to 4-OH TAM. The 4-OH TAM-resistant MCF-7 cells were then transfected with the BAG-1 siRNA and the 4-OH TAM-sensitive MCF-7 cells with the plasmids carrying the human BAG-1 isoform-specific expression constructs respectively to investigate the effect of BAG-1 on the TAM-induced apoptosis.
  
  
  RESULTS
  Our results showed that the TAM-resistant MCF-7 (TAMR/MCF-7) cells expressed higher level of BAG-1 than that of the MCF-7 cells. Down-regulation of BAG-1 significantly enhanced the sensitivity of the TAMR/MCF-7 cells to TAM treatment. Additionally, we found that BAG-1 p50 was the only isoform that inhibited the TAM-induced apoptosis in the MCF-7 cells, while the other isoforms had little effect.
  
  
  CONCLUSIONS
  Our study indicated that up and down regulations of the BAG-1 expression were associated with the decreased and increased sensitivity to 4-OH TAM in the estrogen receptor-positive (ER+) human breast cancer cell line MCF-7 respectively, and distinct isoforms of BAG-1 had different anti-apoptotic ability in breast cancer cells treated with the 4-OH TAM.
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Gao
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Shou-Ching
authors.initials: SC
authors.lastname: Tang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018931:Antineoplastic Agents, Hormonal; C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D014157:Transcription Factors; D013629:Tamoxifen