Cancer Chemotherapy and Pharmacology

, Volume 65, Issue 3, pp 447–455 | Cite as

Gene expression analysis of drug-resistant MCF-7 cells: implications for relation to extracellular matrix proteins

  • Özlem Darcansoy Işeri
  • Meltem Demirel Kars
  • Fikret Arpaci
  • Ufuk Gündüz
Original Article

Abstract

Purpose

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.

Keywords

Multidrug resistance cDNA microarray ECM Integrin MMP ADAM 

Notes

Acknowledgments

We gratefully acknowledge advises of Prof. Dr. Ali Uğur Ural and Prof. Dr. Hüseyin Avni Öktem, and METU Molecular Biology Biotechnology Research Center for technical assistance. This study was supported by TUBITAK (SBAG 3297), Turkey.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Özlem Darcansoy Işeri
    • 1
  • Meltem Demirel Kars
    • 1
  • Fikret Arpaci
    • 2
  • Ufuk Gündüz
    • 1
  1. 1.Department of Biological SciencesMiddle East Technical UniversityAnkaraTurkey
  2. 2.Department of OncologyGülhane Military School of MedicineAnkaraTurkey

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