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Beta-catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells.

Mezhybovska, Maryna LU ; Yudina, Yulyana LU ; Abhyankar, Avinash LU and Sjölander, Anita LU (2009) In British Journal of Cancer 101(9). p.1596-1605
Abstract
BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D(4) (LTD(4)) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD(4) causes translocation of beta-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for beta-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) beta-catenin to analyse its effect... (More)
BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D(4) (LTD(4)) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD(4) causes translocation of beta-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for beta-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) beta-catenin to analyse its effect on mitochondria activity. We have measured the ATP/ADP ratio, and transcription of the mtDNA genes ND2, ND6 and 16 s in these cells stimulated or not with LTD(4). RESULTS: We have shown for the first time that LTD(4) triggers a cellular increase in NADPH dehydrogenase activity and ATP/ADP ratio. In addition, LTD(4) significantly increased the transcription of mtDNA genes. Overexpression of wild-type beta-catenin or a constitutively active beta-catenin mutant mimicked the effect of LTD(4) on ATP/ADP ratio and mtDNA transcription. These elevations in mitochondrial activity resulted in increased reactive oxygen species levels and subsequent activations of the p65 subunit of NF-kappaB. CONCLUSIONS: The present novel data show that LTD(4), presumably through beta-catenin accumulation in the mitochondria, affects mitochondrial activity, lending further credence to the idea that inflammatory signalling pathways are intrinsically linked with potential oncogenic signals. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
101
issue
9
pages
1596 - 1605
publisher
Nature Publishing Group
external identifiers
  • wos:000271247800016
  • pmid:19826421
  • scopus:70350638920
ISSN
1532-1827
DOI
10.1038/sj.bjc.6605342
language
English
LU publication?
yes
id
3c3dc2e8-4a9b-4e12-901c-666698c50d0d (old id 1500375)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19826421?dopt=Abstract
date added to LUP
2009-11-03 15:09:23
date last changed
2017-01-01 07:32:24
@article{3c3dc2e8-4a9b-4e12-901c-666698c50d0d,
  abstract     = {BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D(4) (LTD(4)) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD(4) causes translocation of beta-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for beta-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) beta-catenin to analyse its effect on mitochondria activity. We have measured the ATP/ADP ratio, and transcription of the mtDNA genes ND2, ND6 and 16 s in these cells stimulated or not with LTD(4). RESULTS: We have shown for the first time that LTD(4) triggers a cellular increase in NADPH dehydrogenase activity and ATP/ADP ratio. In addition, LTD(4) significantly increased the transcription of mtDNA genes. Overexpression of wild-type beta-catenin or a constitutively active beta-catenin mutant mimicked the effect of LTD(4) on ATP/ADP ratio and mtDNA transcription. These elevations in mitochondrial activity resulted in increased reactive oxygen species levels and subsequent activations of the p65 subunit of NF-kappaB. CONCLUSIONS: The present novel data show that LTD(4), presumably through beta-catenin accumulation in the mitochondria, affects mitochondrial activity, lending further credence to the idea that inflammatory signalling pathways are intrinsically linked with potential oncogenic signals.},
  author       = {Mezhybovska, Maryna and Yudina, Yulyana and Abhyankar, Avinash and Sjölander, Anita},
  issn         = {1532-1827},
  language     = {eng},
  number       = {9},
  pages        = {1596--1605},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Beta-catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells.},
  url          = {http://dx.doi.org/10.1038/sj.bjc.6605342},
  volume       = {101},
  year         = {2009},
}