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Updated: Jun 22, 2026
Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer
Published on: May 21, 2019
Gene expression analysis of drug-resistant MCF-7 cells: implications for relation to extracellular matrix proteins
Ozlem Darcansoy Işeri1, Meltem Demirel Kars, Fikret Arpaci
1Department of Biological Sciences, Middle East Technical University, 06531, Ankara, Turkey. odiseri@baskent.edu.tr
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.
Insights
Drug resistance in cancer cells alters genes involved in the extracellular matrix (ECM), impacting cell behavior. This study identified specific ECM and matrix-degrading enzyme gene expression changes in resistant breast cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Multidrug resistance (MDR) in cancer is a complex challenge.
- The extracellular matrix (ECM) plays a critical role in tumor cell proliferation, invasion, and metastasis.
Purpose of the Study:
- To investigate alterations in gene expression profiles of ECM components and related enzymes in drug-resistant breast cancer cells.
- To identify potential new genes contributing to multidrug resistance using large-scale expression analysis.
Main Methods:
- Development of drug-resistant MCF-7 breast cancer cell lines through stepwise selection.
- High-density oligonucleotide microarrays (Affymetrix GeneChip) for global gene expression profiling.
- Statistical analysis using independent sample t-tests and volcano plots for gene filtering.
Main Results:
- Upregulation of 25 genes encoding ECM proteins (e.g., collagen, fibronectin, syndecan) and integrin receptors in drug-resistant cells.
- Altered expression of 13 genes encoding matrix metalloproteinases (MMPs), adamalysins (ADAMs, ADAMTSs), and tissue inhibitors of metalloproteinases (TIMPs), including MMP1, MMP9, ADAM9, and TIMP3.
- Identification of significant gene expression changes in drug-resistant MCF-7 sublines compared to sensitive cells.
Conclusions:
- Drug resistance in breast cancer is associated with significant changes in the expression of ECM components and related proteases.
- These findings suggest a link between ECM remodeling and the development of multidrug resistance, potentially influencing invasion and metastasis.
- Further research is needed to elucidate the specific role of individual ECM components in mediating drug resistance.
