Differentially Expressed Mitochondrial Proteins in Human MCF7 Breast Cancer Cells Resistant to Paclitaxel
Language English Country Switzerland Media electronic
Document type Journal Article
Grant support
664216
Grantová Agentura, Univerzita Karlova
19-03063S
Grantová Agentura České Republiky
PubMed
31248089
PubMed Central
PMC6628585
DOI
10.3390/ijms20122986
PII: ijms20122986
Knihovny.cz E-resources
- Keywords
- ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, 3B), abhydrolase-domain containing protein 11 (ABHD11), breast cancer cells, carbamoyl-phosphate synthetase 1 (CPS1), cathepsin D, mitochondria, paclitaxel resistance, two-dimensional electrophoresis,
- MeSH
- Drug Resistance, Neoplasm * drug effects MeSH
- Cell Fractionation MeSH
- Carbamoyl-Phosphate Synthase (Ammonia) genetics metabolism MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Mitochondrial Proteins genetics metabolism MeSH
- Mitochondria genetics metabolism MeSH
- Breast Neoplasms drug therapy genetics metabolism MeSH
- Paclitaxel pharmacology MeSH
- Proteome MeSH
- Proteomics methods MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Tandem Mass Spectrometry MeSH
- Gene Silencing MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- CPS1 protein, human MeSH Browser
- Carbamoyl-Phosphate Synthase (Ammonia) MeSH
- Mitochondrial Proteins MeSH
- Paclitaxel MeSH
- Proteome MeSH
Identification of novel proteins with changed expression in resistant cancer cells could be helpful in elucidation mechanisms involved in the development of acquired resistance to paclitaxel. In this study, we carried out a 2D-PAGE using the mitochondrial-enriched fraction from paclitaxel-resistant MCF7/PacR cells compared to original paclitaxel-sensitive MCF7 breast cancer cells. Differentially expressed proteins were identified employing mass spectrometry. We found that lysosomal cathepsin D and mitochondrial abhydrolase-domain containing protein 11 (ABHD11) had decreased expression in MCF7/PacR cells. On the other hand, mitochondrial carbamoyl-phosphate synthetase 1 (CPS1) and ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, ATAD3B) were overexpressed in MCF7/PacR cells. Further, we showed that there was no difference in localization of CPS1 in MCF7 and MCF7/PacR cells. We demonstrated a significant increase in the number of CPS1 positive MCF7/PacR cells, using FACS analysis, compared to the number of CPS1 positive MCF7 cells. Silencing of CPS1 expression by specific siRNA had no significant effect on the resistance of MCF7/PacR cells to paclitaxel. To summarize, we identified several novel proteins of a mitochondrial fraction whose role in acquired resistance to paclitaxel in breast cancer cells should be further assessed.
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