title: Gene expression analysis of drug-resistant MCF-7 cells: implications for relation to extracellular matrix proteins.
abstract: OBJECTIVE
  Since multidrug resistance is a multifactorial phenomenon, a large-scale expression analysis of drug-resistant cells by using high-density oligonucleotide microarrays may provide information about new candidate genes contributing to resistance. Extracellular matrix (ECM) is responsible for many aspects of proliferation and invasive/metastatic behavior of tumor cells. This study demonstrates alterations in gene expression levels of several ECM components, matrix metalloproteinases (MMPs), adamalysins (ADAMs and ADAMTSs) and tissue inhibitors of metalloproteinases (TIMPs) in paclitaxel, docetaxel, vincristine and doxorubicin-resistant MCF-7 cells.
  
  
  METHODS
  Resistant MCF-7 cells were developed by stepwise selection of cells in increasing concentrations of drugs. Affymetrix GeneChip Human Genome U133 Plus 2.0 Array was used for hybridizations. Statistical significance was determined by independent sample t test. The genes having altered expression levels in drug-resistant sublines were selected and filtered by volcano plots.
  
  
  RESULTS
  Genes up/downregulated more than twofolds were selected and listed. Expression of 25 genes encoding ECM proteins (including collagen, finronectin and syndecan) and integrin receptor subunits were found to be upregulated in drug-resistant cells. In addition, expression levels of, 13 genes encoding MMPs, ADAMs, ADAMTSs and TIMPs (including MMP1, MMP9, ADAM9 and TIMP3) were found to be altered in drug-resistant sublines when compared with sensitive MCF-7.
  
  
  CONCLUSIONS
  Based on the expression analysis profiles, this report provides a preliminary insight into the relationship between drug resistance and ECM components, which are related to invasion and metastasis. Correlation of each specific ECM component with drug resistance requires further analysis.
authors: Department of Biological Sciences, Middle East Technical University, 06531, Ankara, Turkey. odiseri@baskent.edu.tr
authors: Ozlem Darcansoy
authors: OD
authors: Işeri
authors: Meltem Demirel
authors: MD
authors: Kars
authors: Fikret
authors: F
authors: Arpaci
authors: Ufuk
authors: U
authors: Gündüz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017239:Paclitaxel / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D043823:Taxoids; D000077143:Docetaxel; D014750:Vincristine; D004317:Doxorubicin; D017239:Paclitaxel