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Updated: Jun 5, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Drug resistant MCF-7 cells exhibit epithelial-mesenchymal transition gene expression pattern
Ozlem Darcansoy Işeri1, Meltem Demirel Kars, Fikret Arpaci
1Middle East Technical University, Department of Biological Sciences, 06531 Ankara, Turkey.
Purpose:
Multidrug resistance is resistance to structurally unrelated anticancer agents. Large-scale expression analysis by using high-density oligonucleotide microarrays may provide information about new candidate genes contributing to MDR. This study demonstrates alterations in expression levels of several genes related to epithelial-mesenchymal transition (EMT) in paclitaxel, docetaxel, and doxorubicin resistant MCF-7 cells.
Methods:
Resistant sublines were developed from sensitive cells by selective paclitaxel, docetaxel, and doxorubicin applications in dose increments. cDNA microarray analysis was performed for sensitive and resistant cells. Genes having statistically significantly altered expression levels more than two-folds compared to the sensitive MCF-7 cells were considered. Genes encoding the determinants of the EMT were evaluated. Immunostaining was performed for relevant protein expressions.
Results:
Key elements of EMT were transcriptionally activated in paclitaxel, docetaxel and doxorubicin resistant sublines. One of the upregulated genes was Slug, a transcription factor of E-cadherin, occludin repression, and N-cadherin, vimentin activation. Decreased estrogen receptor-α (ER) levels in cells might have stimulated Slug expression. Increased expression levels of TGF-beta receptor2 (TGFBR2) together with SMAD3 might have stimulated EMT in resistant cells. Immunocytochemistry results confirmed loss of ER and E-cadherin, together with high vimentin levels.
Conclusions:
EMT was induced in multidrug resistant MCF-7 cells indicating a relationship of this process and drug resistance. However, the relationship of each specific component of EMT with drug resistance requires further analysis.
Insights
Multidrug resistance (MDR) in cancer cells involves changes in genes related to epithelial-mesenchymal transition (EMT). This study found EMT markers are activated in resistant cells, suggesting a link between EMT and MDR.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Multidrug resistance (MDR) poses a significant challenge in cancer therapy, characterized by resistance to structurally unrelated anticancer agents.
- Understanding the molecular mechanisms underlying MDR is crucial for developing effective treatment strategies.
- Gene expression analysis offers a powerful approach to identify novel targets contributing to MDR.
Purpose of the Study:
- To investigate alterations in gene expression profiles associated with multidrug resistance in MCF-7 breast cancer cells.
- To identify specific genes, particularly those involved in epithelial-mesenchymal transition (EMT), that are dysregulated in resistant cell lines.
- To explore the potential role of EMT in the development of paclitaxel, docetaxel, and doxorubicin resistance.
Main Methods:
- Development of multidrug-resistant MCF-7 sublines through incremental exposure to paclitaxel, docetaxel, and doxorubicin.
- High-density oligonucleotide microarray analysis to compare gene expression between sensitive and resistant cells.
- Identification of genes with statistically significant expression changes ( > 2-fold) and evaluation of EMT-related gene determinants.
- Confirmation of protein expression changes using immunostaining and immunocytochemistry.
Main Results:
- Key genes associated with EMT were transcriptionally activated in paclitaxel, docetaxel, and doxorubicin-resistant MCF-7 cells.
- Upregulation of the transcription factor Slug was observed, leading to repression of E-cadherin and occludin, and activation of N-cadherin and vimentin.
- Decreased estrogen receptor-alpha (ER) levels may have contributed to Slug upregulation, while increased TGF-beta receptor 2 (TGFBR2) and SMAD3 expression potentially promoted EMT.
- Immunocytochemistry confirmed reduced ER and E-cadherin expression, alongside elevated vimentin levels.
Conclusions:
- Epithelial-mesenchymal transition (EMT) is induced in multidrug-resistant MCF-7 cells, indicating a significant relationship between EMT and the development of drug resistance.
- Further research is necessary to elucidate the specific contribution of each EMT component to multidrug resistance.
- These findings highlight EMT as a potential therapeutic target for overcoming drug resistance in breast cancer.
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