Gene expression analysis of drug-resistant MCF-7 cells: implications for relation to extracellular matrix proteins.
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.
Işeri
Ozlem Darcansoy
OD
Department of Biological Sciences, Middle East Technical University, 06531, Ankara, Turkey. odiseri@baskent.edu.tr
Kars
Meltem Demirel
MD
Arpaci
Fikret
F
Gündüz
Ufuk
U
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
D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D043823:Taxoids; D000077143:Docetaxel; D014750:Vincristine; D004317:Doxorubicin; D017239:Paclitaxel