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Subcutaneous Ehrlich Ascites Carcinoma mice model for studying cancer-induced cardiomyopathy

Mishra, S and Tamta, AK and Sarikhani, M and Desingu, PA and Kizkekra, SM and Pandit, AS and Kumar, S and Khan, D and Raghavan, SC and Sundaresan, NR (2018) Subcutaneous Ehrlich Ascites Carcinoma mice model for studying cancer-induced cardiomyopathy. In: Scientific Reports, 8 (1).

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Official URL: https://doi.org/10.1038/s41598-018-23669-9


Cardiomyopathy is one of the characteristic features of cancer. In this study, we establish a suitable model to study breast cancer-induced cardiomyopathy in mice. We used Ehrlich Ascites Carcinoma cells to induce subcutaneous tumor in 129/SvJ mice and studied its effect on heart function. In Ehrlich Ascites Carcinoma bearing mice, we found significant reduction in left ventricle wall thickness, ejection fraction, and fractional shortening increase in left ventricle internal diameter. We found higher muscle atrophy, degeneration, fibrosis, expression of cell-adhesion molecules and cell death in tumor-bearing mice hearts. As observed in cancer patients, we found that mTOR, a key signalling molecule responsible for maintaining cell growth and autophagy was suppressed in this model. Tumor bearing mice hearts show increased expression and nuclear localization of TFEB and FoxO3a transcription factors, which are involved in the upregulation of muscle atrophy genes, lysosomal biogenesis genes and autophagy genes. We propose that Ehrlich Ascites Carcinoma induced tumor can be used as a model to identify potential therapeutic targets for the treatment of heart failure in patients suffering from cancer-induced cardiomyopathy. This model can also be used to test the adverse consequences of cancer chemotherapy in heart.

Item Type: Journal Article
Publication: Scientific Reports
Publisher: Nature Publishing Group
Additional Information: The copyright for this article belongs to the Authors.
Keywords: basic helix loop helix leucine zipper transcription factor; beclin 1; FoxO3 protein, mouse; mTOR protein, mouse; target of rapamycin kinase; Tcfeb protein, mouse; transcription factor FKHRL1, 129 mouse; animal; autophagy; cachexia; cardiac muscle; cardiomyopathy; complication; disease model; Ehrlich ascites tumor; fibrosis; genetics; lysosome; metabolism; mouse; pathology, Animals; Autophagy; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Beclin-1; Cachexia; Carcinoma, Ehrlich Tumor; Cardiomyopathies; Disease Models, Animal; Fibrosis; Forkhead Box Protein O3; Lysosomes; Mice; Mice, 129 Strain; Myocardium; TOR Serine-Threonine Kinases
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 23 Aug 2022 10:36
Last Modified: 23 Aug 2022 10:36
URI: https://eprints.iisc.ac.in/id/eprint/76207

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