title: Overexpression of molecular chaperons GRP78 and GRP94 in CD44(hi)/CD24(lo) breast cancer stem cells.
abstract: BACKGROUND
  Breast cancer stem cell with CD44(hi)/CD24(lo) phonotype is described having stem cell properties and represented as the main driving factor in breast cancer initiation, growth, metastasis and low response to anti-cancer agents. Glucoseregulated proteins (GRPs) are heat shock protein family chaperons that are charged with regulation of protein machinery and modulation of endoplasmic reticulum homeostasis whose important roles in stem cell development and invasion of various cancers have been demonstrated. Here, we investigated the expression levels of GRP78 and GRP94 in CD44(hi)/CD24(lo) phenotype breast cancer stem cells (BCSCs).
  
  
  METHODS
  MCF7, T-47D and MDA-MB-231 breast cancer cell lines were used. CD44(hi)/CD24(lo) phenotype cell population were analyzed and sorted by fluorescence-activated cell sorting (FACS). Transcriptional and translational expression of GRP78 and GRP94 were investigated by western blotting and quantitative real time PCR.
  
  
  RESULTS
  RESULTS showed different proportion of CD44(hi)/CD24(lo) phenotype cell population in their original bulk cells. The ranking of the cell lines in terms of CD44(hi)/CD24(lo) phenotype cell population was as MCF7<T-47D<MDA-MB-231. Our results also indicated that CD44(hi)/CD24(lo) phenotype cells exhibited higher mRNA and protein expression level of GRP78 and GRP94 compared to their original bulk cells.
  
  
  CONCLUSIONS
  Our results show a relationship between overexpression of GRP78 and GRP94 and exhibiting CD44hi/CD24lo phenotype in breast cancer cells. We conclude that upregulation of GRPs may be an important factor in the emergence of CD44hi/CD24lo phenotype BCSCs features.
authors.affiliation: Department of Medical Genetics and The Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Babak
authors.initials: B
authors.lastname: Nami
authors.affiliation: Department of Microbiology, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Armin
authors.initials: A
authors.lastname: Ghasemi-Dizgah
authors.affiliation: Young Researchers and Elite Club, Ardabil Branch, Islamic Azad University, Ardabil, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Vaseghi
keywords: Breast cancer; Cancer stem cell; GRP78; GRP94; Overexpression