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Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients
Author(s) -
Magnusson Cecilia,
Liu Jian,
Ehrnström Roy,
Manjer Jonas,
Jirström Karin,
Andersson Tommy,
Sjölander Anita
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25648
Subject(s) - breast cancer , hazard ratio , tamoxifen , medicine , tumor progression , cancer , cancer research , oncology , receptor , confidence interval
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 proinflammatory 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 (hazard ratio [HR] = 2.88, 95% confidence interval [CI] = 1.11–7.41), as well as patients with large (>20 mm) 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 (>20 mm) tumors, elevated CysLT 2 R expression predicted an improved 5‐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 estrogene receptor‐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 This elevated CysLT 2 R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn.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.