ABCG2 Overexpression Contributes to Pevonedistat Resistance
Abstract
:1. Introduction
2. Results
2.1. Generation of a Novel MLN4924 Resistant Ovarian Cancer Model System
2.2. ABCG2 is Highly Upregulated in MLN4924-Resistant Cells
2.3. Targeting ABCG2 Overexpression Diminishes Resistance to MLN4924
2.4. Mitoxantrone-Selected ABCG2-Overexpressing Cells are Resistant to MLN4924
2.5. ABCG2 Overexpression is Sufficient to Confer Resistance to MLN4924
2.6. MLN4924 Stimulates ABCG2 ATPase Activity
2.7. Docking Analysis of MLN4924 with Human ABCG2
3. Discussion
4. Materials and Methods
4.1. Cells and Cell Culture
4.2. Antibodies and Reagents
4.3. Quantification of Drug-Induced Cytotoxicity
4.4. Mutation Analysis of NAEβ (UBA3) in A2780 and A2780/MLN-R Cells
4.5. Transcriptome Profiling
4.6. Immunoblotting
4.7. qRT-PCR
4.8. shRNA Knockdown of ABCG2
4.9. ATPase Activity of ABCG2
4.10. Molecular Modeling of Human ABCG2 and Docking of MLN4924
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Kathawala, R.J.; Espitia, C.M.; Jones, T.M.; Islam, S.; Gupta, P.; Zhang, Y.-K.; Chen, Z.-S.; Carew, J.S.; Nawrocki, S.T. ABCG2 Overexpression Contributes to Pevonedistat Resistance. Cancers 2020, 12, 429. https://doi.org/10.3390/cancers12020429
Kathawala RJ, Espitia CM, Jones TM, Islam S, Gupta P, Zhang Y-K, Chen Z-S, Carew JS, Nawrocki ST. ABCG2 Overexpression Contributes to Pevonedistat Resistance. Cancers. 2020; 12(2):429. https://doi.org/10.3390/cancers12020429
Chicago/Turabian StyleKathawala, Rishil J., Claudia M. Espitia, Trace M. Jones, Shariful Islam, Pranav Gupta, Yun-Kai Zhang, Zhe-Sheng Chen, Jennifer S. Carew, and Steffan T. Nawrocki. 2020. "ABCG2 Overexpression Contributes to Pevonedistat Resistance" Cancers 12, no. 2: 429. https://doi.org/10.3390/cancers12020429