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Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.

Magnusson, Cecilia LU ; Liu, Jian LU ; Ehrnström, Roy LU ; Manjer, Jonas LU ; Jirström, Karin LU ; Andersson, Tommy LU and Sjölander, Anita LU (2011) In International Journal of Cancer Okt. p.9-22
Abstract
The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with... (More)
The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI 1.83-30.8). In patients with large (>20mm) tumors, elevated CysLT(2)R expression predicted an improved five-year survival (log-rank test P = 0.04). Surprisingly, for longer time periods this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in ER-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
Okt
pages
9 - 22
publisher
John Wiley & Sons
external identifiers
  • wos:000289987300002
  • pmid:20824707
  • scopus:79955420164
ISSN
0020-7136
DOI
10.1002/ijc.25648
language
English
LU publication?
yes
id
515b179d-1490-407a-b31a-15f3066cec85 (old id 1688428)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20824707?dopt=Abstract
date added to LUP
2010-10-05 09:45:42
date last changed
2017-08-27 05:44:37
@article{515b179d-1490-407a-b31a-15f3066cec85,
  abstract     = {The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here we have determined the expression of pro-inflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (HR = 2.88, 95% CI 1.11-7.41), as well as patients with large (>20mm) tumors (HR = 5.08, 95% CI 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI 1.83-30.8). In patients with large (>20mm) tumors, elevated CysLT(2)R expression predicted an improved five-year survival (log-rank test P = 0.04). Surprisingly, for longer time periods this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in ER-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients.},
  author       = {Magnusson, Cecilia and Liu, Jian and Ehrnström, Roy and Manjer, Jonas and Jirström, Karin and Andersson, Tommy and Sjölander, Anita},
  issn         = {0020-7136},
  language     = {eng},
  pages        = {9--22},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.},
  url          = {http://dx.doi.org/10.1002/ijc.25648},
  volume       = {Okt},
  year         = {2011},
}