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Comparative proteomic analysis of paclitaxel resistance-related proteins in human breast cancer cell lines
Hiroya Fujioka1, Akiko Sakai2, Satoru Tanaka1
1Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Abstract:
Paclitaxel is widely used to treat various cancers; however, resistance to this drug is a major obstacle to breast cancer chemotherapy. To identify the proteins involved in paclitaxel resistance, the present study compared the proteomes of MCF-7 human breast cancer cells and its paclitaxel-resistant subclone MCF-7/PTX. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry, 11 upregulated and 12 downregulated proteins were identified in MCF-7/PTX cells compared with the parental cell line. These 23 proteins were functionally classified as stress-induced chaperones, metabolic enzymes and cytoskeletal proteins. The anti-apoptotic proteins, stress-70 protein, 78-kD glucose-regulated protein, peptidyl-prolyl cis-trans isomerase A (PPIA) and heterogeneous nuclear ribonucleoprotein H3, were also upregulated in MCF-7/PTX cells. Notably, knockdown of the stress-response chaperone PPIA using small interfering RNA in MCF-7/PTX cells restored their sensitivity to paclitaxel. These findings indicated that PPIA may have an important role in paclitaxel resistance in MCF-7/PTX cells.
Insights
Paclitaxel resistance in breast cancer is a challenge. Researchers found that peptidyl-prolyl cis-trans isomerase A (PPIA) is upregulated in resistant cells and restoring sensitivity to paclitaxel.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Paclitaxel is a vital chemotherapy drug for various cancers.
- Drug resistance, particularly in breast cancer, limits paclitaxel's efficacy.
- Identifying proteins associated with paclitaxel resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To compare proteomes of paclitaxel-sensitive (MCF-7) and paclitaxel-resistant (MCF-7/PTX) human breast cancer cells.
- To identify specific proteins contributing to paclitaxel resistance.
- To investigate the role of upregulated proteins in mediating resistance.
Main Methods:
- Proteomic analysis using two-dimensional gel electrophoresis (2D-PAGE).
- Protein identification via matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS).
- Functional classification of identified proteins and validation using small interfering RNA (siRNA) knockdown.
Main Results:
- 11 proteins were upregulated and 12 downregulated in MCF-7/PTX cells compared to MCF-7 cells.
- Upregulated proteins included stress-induced chaperones, metabolic enzymes, and cytoskeletal proteins.
- Peptidyl-prolyl cis-trans isomerase A (PPIA), an anti-apoptotic protein, was notably upregulated.
Conclusions:
- PPIA is upregulated in paclitaxel-resistant breast cancer cells.
- Knockdown of PPIA using siRNA resensitized MCF-7/PTX cells to paclitaxel.
- PPIA plays a significant role in mediating paclitaxel resistance in breast cancer.
