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

• Published in: Cancer chemotherapy and pharmacology Vol. 65; no. 3; pp. 447 - 455
• Main Authors: Işeri, Özlem Darcansoy, Kars, Meltem Demirel, Arpaci, Fikret, Gündüz, Ufuk
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.02.2010; Springer-Verlag; Springer; Springer Nature B.V
• 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; MMP; ADAM; cDNA microarray; Integrin; Multidrug resistance; ECM; Treatment resistance; Enzyme; Cell adhesion molecule; DNA chip; Metalloendopeptidases; Gene expression; In vitro; Peptidases; Adamalysin; Analysis; Multiple resistance; A disintegrin and metalloproteinases; Established cell line; Hydrolases; Extracellular matrix; Cell
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-1048-z

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.