title: Drug resistant MCF-7 cells exhibit epithelial-mesenchymal transition gene expression pattern.
abstract: OBJECTIVE
  Multidrug resistance is resistance to structurally unrelated anticancer agents. Large-scale expression analysis by using high-density oligonucleotide microarrays may provide information about new candidate genes contributing to MDR. This study demonstrates alterations in expression levels of several genes related to epithelial-mesenchymal transition (EMT) in paclitaxel, docetaxel, and doxorubicin resistant MCF-7 cells.
  
  
  METHODS
  Resistant sublines were developed from sensitive cells by selective paclitaxel, docetaxel, and doxorubicin applications in dose increments. cDNA microarray analysis was performed for sensitive and resistant cells. Genes having statistically significantly altered expression levels more than two-folds compared to the sensitive MCF-7 cells were considered. Genes encoding the determinants of the EMT were evaluated. Immunostaining was performed for relevant protein expressions.
  
  
  RESULTS
  Key elements of EMT were transcriptionally activated in paclitaxel, docetaxel and doxorubicin resistant sublines. One of the upregulated genes was Slug, a transcription factor of E-cadherin, occludin repression, and N-cadherin, vimentin activation. Decreased estrogen receptor-α (ER) levels in cells might have stimulated Slug expression. Increased expression levels of TGF-beta receptor2 (TGFBR2) together with SMAD3 might have stimulated EMT in resistant cells. Immunocytochemistry results confirmed loss of ER and E-cadherin, together with high vimentin levels.
  
  
  CONCLUSIONS
  EMT was induced in multidrug resistant MCF-7 cells indicating a relationship of this process and drug resistance. However, the relationship of each specific component of EMT with drug resistance requires further analysis.
authors.affiliation: Middle East Technical University, Department of Biological Sciences, 06531 Ankara, Turkey.
authors.forename: Ozlem Darcansoy
authors.initials: OD
authors.lastname: Işeri
authors.forename: Meltem Demirel
authors.initials: MD
authors.lastname: Kars
authors.forename: Fikret
authors.initials: F
authors.lastname: Arpaci
authors.forename: Can
authors.initials: C
authors.lastname: Atalay
authors.forename: Işin
authors.initials: I
authors.lastname: Pak
authors.forename: Ufuk
authors.initials: U
authors.lastname: Gündüz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry