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

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 m...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2010-02, Vol.65 (3), p.447-455
Main Authors: Işeri, Özlem Darcansoy, Kars, Meltem Demirel, Arpaci, Fikret, Gündüz, Ufuk
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer Research
Cell Line, Tumor
Cluster Analysis
Doxorubicin - pharmacology
Drug Resistance, Neoplasm - genetics
Extracellular Matrix Proteins - genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic - drug effects
Humans
Medical sciences
Medicine
Medicine & Public Health
Oligonucleotide Array Sequence Analysis - methods
Oncology
Original Article
Paclitaxel - pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Taxoids - pharmacology
Vincristine - pharmacology
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Summary: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.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-009-1048-z