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Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma

BACKGROUND: The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression. METHODS: To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma un...

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Autores principales: Ananieva, Elitsa A., Bostic, Joshua N., Torres, Ashley A., Glanz, Hannah R., McNitt, Sean M., Brenner, Michelle K., Boyer, Michael P., Addington, Adele K., Hutson, Susan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203766/
https://www.ncbi.nlm.nih.gov/pubmed/30318512
http://dx.doi.org/10.1038/s41416-018-0283-7
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author Ananieva, Elitsa A.
Bostic, Joshua N.
Torres, Ashley A.
Glanz, Hannah R.
McNitt, Sean M.
Brenner, Michelle K.
Boyer, Michael P.
Addington, Adele K.
Hutson, Susan M.
author_facet Ananieva, Elitsa A.
Bostic, Joshua N.
Torres, Ashley A.
Glanz, Hannah R.
McNitt, Sean M.
Brenner, Michelle K.
Boyer, Michael P.
Addington, Adele K.
Hutson, Susan M.
author_sort Ananieva, Elitsa A.
collection PubMed
description BACKGROUND: The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression. METHODS: To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma under different diet compositions with varying amounts of branched-chain amino acids (BCAAs). Next, the growth and metabolism of EL-4 cells were studied in the presence of different leucine concentrations in the growth medium. RESULTS: BCATmKO mice experienced delayed tumour growth when fed standard rodent chow or a normal BCAA diet. Tumour suppression correlated with 37.6- and 18.9-fold increases in plasma and tumour BCAAs, 37.5% and 30.4% decreases in tumour glutamine and alanine, and a 3.5-fold increase in the phosphorylation of tumour AMPK in BCATmKO mice on standard rodent chow. Similar results were obtained with a normal but not with a choice BCAA diet. CONCLUSIONS: Global deletion of BCATm caused a dramatic build-up of BCAAs, which could not be utilised for energy or amino acid synthesis, ultimately delaying the growth of lymphoma tumours. Furthermore, physiological, but not high, leucine concentrations promoted the growth of EL-4 cells. BCATm and BCAA metabolism were identified as attractive targets for anti-lymphoma therapy.
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spelling pubmed-62037662019-10-15 Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma Ananieva, Elitsa A. Bostic, Joshua N. Torres, Ashley A. Glanz, Hannah R. McNitt, Sean M. Brenner, Michelle K. Boyer, Michael P. Addington, Adele K. Hutson, Susan M. Br J Cancer Article BACKGROUND: The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression. METHODS: To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma under different diet compositions with varying amounts of branched-chain amino acids (BCAAs). Next, the growth and metabolism of EL-4 cells were studied in the presence of different leucine concentrations in the growth medium. RESULTS: BCATmKO mice experienced delayed tumour growth when fed standard rodent chow or a normal BCAA diet. Tumour suppression correlated with 37.6- and 18.9-fold increases in plasma and tumour BCAAs, 37.5% and 30.4% decreases in tumour glutamine and alanine, and a 3.5-fold increase in the phosphorylation of tumour AMPK in BCATmKO mice on standard rodent chow. Similar results were obtained with a normal but not with a choice BCAA diet. CONCLUSIONS: Global deletion of BCATm caused a dramatic build-up of BCAAs, which could not be utilised for energy or amino acid synthesis, ultimately delaying the growth of lymphoma tumours. Furthermore, physiological, but not high, leucine concentrations promoted the growth of EL-4 cells. BCATm and BCAA metabolism were identified as attractive targets for anti-lymphoma therapy. Nature Publishing Group UK 2018-10-15 2018-10-16 /pmc/articles/PMC6203766/ /pubmed/30318512 http://dx.doi.org/10.1038/s41416-018-0283-7 Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Ananieva, Elitsa A.
Bostic, Joshua N.
Torres, Ashley A.
Glanz, Hannah R.
McNitt, Sean M.
Brenner, Michelle K.
Boyer, Michael P.
Addington, Adele K.
Hutson, Susan M.
Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title_full Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title_fullStr Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title_full_unstemmed Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title_short Mice deficient in the mitochondrial branched-chain aminotransferase (BCATm) respond with delayed tumour growth to a challenge with EL-4 lymphoma
title_sort mice deficient in the mitochondrial branched-chain aminotransferase (bcatm) respond with delayed tumour growth to a challenge with el-4 lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203766/
https://www.ncbi.nlm.nih.gov/pubmed/30318512
http://dx.doi.org/10.1038/s41416-018-0283-7
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