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Endogenous production of leukotriene D(4) mediates autocrine survival and proliferation via CysLT(1) receptor signalling in intestinal epithelial cells.

Paruchuri, Sailaja LU ; Mezhybovska, Maryna LU ; Juhas, Maria LU and Sjölander, Anita LU (2006) In Oncogene 25(50). p.6660-6665
Abstract
The cysteinyl leukotriene(1) (CysLT(1)) receptor (CysLT(1)R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour-and tumour-derived intestinal epithelial cells. Treatment of two non-tumour cell lines, Int 407 and IEC-6, with CysLT1R antagonists led to shrinkage and detachment of cells, confirmed as apoptotic cell death, and a dose-dependent reduction in proliferation. However, in the tumour intestinal cell lines Caco-2, SW480, HCT-116 and HT-29, treatment with CysLT1R antagonists significantly reduced proliferation, but had no effect on apoptosis. A unique characteristic of intestinal cancer cells is the... (More)
The cysteinyl leukotriene(1) (CysLT(1)) receptor (CysLT(1)R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour-and tumour-derived intestinal epithelial cells. Treatment of two non-tumour cell lines, Int 407 and IEC-6, with CysLT1R antagonists led to shrinkage and detachment of cells, confirmed as apoptotic cell death, and a dose-dependent reduction in proliferation. However, in the tumour intestinal cell lines Caco-2, SW480, HCT-116 and HT-29, treatment with CysLT1R antagonists significantly reduced proliferation, but had no effect on apoptosis. A unique characteristic of intestinal cancer cells is the presence of nuclear CysLT(1)Rs, which are inaccessible to receptor antagonists. In these cells, inhibition of the endogenous production of CysLTs indirectly, by 5-lipoxygenase inhibition, impaired CysLT1R signalling throughout the cell, and resulted in apoptosis of the tumour cells. These data reveal the existence of constitutive CysLT1R signalling that mediates both survival and proliferation in intestinal cells. Importantly, we propose that tumour-derived intestinal cells are resistant to CysLT(1)R antagonist-induced apoptosis, a phenomena that could be explained by nuclear CysLT1R signalling. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
caspase-3, apoptosis, epithelial cells, CysLT(1) receptor
in
Oncogene
volume
25
issue
50
pages
6660 - 6665
publisher
Nature Publishing Group
external identifiers
  • wos:000241569700010
  • scopus:33750469042
ISSN
1476-5594
DOI
10.1038/sj.onc.1209666
language
English
LU publication?
yes
id
d74af474-7da3-4134-b544-f1969642f1c0 (old id 156646)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16715140&dopt=Abstract
date added to LUP
2016-04-01 12:00:35
date last changed
2021-05-25 02:08:01
@article{d74af474-7da3-4134-b544-f1969642f1c0,
  abstract     = {The cysteinyl leukotriene(1) (CysLT(1)) receptor (CysLT(1)R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour-and tumour-derived intestinal epithelial cells. Treatment of two non-tumour cell lines, Int 407 and IEC-6, with CysLT1R antagonists led to shrinkage and detachment of cells, confirmed as apoptotic cell death, and a dose-dependent reduction in proliferation. However, in the tumour intestinal cell lines Caco-2, SW480, HCT-116 and HT-29, treatment with CysLT1R antagonists significantly reduced proliferation, but had no effect on apoptosis. A unique characteristic of intestinal cancer cells is the presence of nuclear CysLT(1)Rs, which are inaccessible to receptor antagonists. In these cells, inhibition of the endogenous production of CysLTs indirectly, by 5-lipoxygenase inhibition, impaired CysLT1R signalling throughout the cell, and resulted in apoptosis of the tumour cells. These data reveal the existence of constitutive CysLT1R signalling that mediates both survival and proliferation in intestinal cells. Importantly, we propose that tumour-derived intestinal cells are resistant to CysLT(1)R antagonist-induced apoptosis, a phenomena that could be explained by nuclear CysLT1R signalling.},
  author       = {Paruchuri, Sailaja and Mezhybovska, Maryna and Juhas, Maria and Sjölander, Anita},
  issn         = {1476-5594},
  language     = {eng},
  number       = {50},
  pages        = {6660--6665},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Endogenous production of leukotriene D(4) mediates autocrine survival and proliferation via CysLT(1) receptor signalling in intestinal epithelial cells.},
  url          = {http://dx.doi.org/10.1038/sj.onc.1209666},
  doi          = {10.1038/sj.onc.1209666},
  volume       = {25},
  year         = {2006},
}