Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Experiments
2.2. Genotyping
2.3. DEN Administration and Sample Collection
2.4. Liver Tumor Analysis
2.5. Immunohistochemical (IHC) Staining and Review
2.6. Western Blot Assays
2.7. Real-Time PCR
2.8. RT-PCR Data Pretreatment/Transformation
2.9. Metabolome Analysis
2.10. Statistical Analysis
3. Results
3.1. Aldh1l1 Knockout Alters Tumor Growth Dynamics in a DEN Model Of Carcinogenesis
3.2. Large Tumors in DEN-Treated Wild-Type Mice Lost ALDH1L1 Protein
3.3. Vascular Density in Livers of Aldh1l1−/− and Aldh1l1+/+ Mice
3.4. Expression of Cancer-Related Genes in DEN-Treated Mice
3.5. Aldh1l1−/− Mice Demonstrate an Altered Metabolic Response to DEN Compared To Wild-Type Mice
3.5.1. Overall Metabolic Changes
3.5.2. Folates and Related Metabolites
3.5.3. Acylglycine Conjugates
3.5.4. Monoacylglycerols and Fatty Acids
3.5.5. Carbohydrates
3.5.6. Redox Homeostasis Metabolites
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Krupenko, N.I.; Sharma, J.; Fogle, H.M.; Pediaditakis, P.; Strickland, K.C.; Du, X.; Helke, K.L.; Sumner, S.; Krupenko, S.A. Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis. Cancers 2021, 13, 3219. https://doi.org/10.3390/cancers13133219
Krupenko NI, Sharma J, Fogle HM, Pediaditakis P, Strickland KC, Du X, Helke KL, Sumner S, Krupenko SA. Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis. Cancers. 2021; 13(13):3219. https://doi.org/10.3390/cancers13133219
Chicago/Turabian StyleKrupenko, Natalia I., Jaspreet Sharma, Halle M. Fogle, Peter Pediaditakis, Kyle C. Strickland, Xiuxia Du, Kristi L. Helke, Susan Sumner, and Sergey A. Krupenko. 2021. "Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis" Cancers 13, no. 13: 3219. https://doi.org/10.3390/cancers13133219