Maria Riedmeier1, Maciej Skrzypczak2, Susanne Schüler-Toprak1, Olaf Ortmann1, Oliver Treeck3. 1. Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany. 2. Second Department of Gynecology, Medical University of Lublin, Lublin, Poland. 3. Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany. otreeck@caritasstjosef.de.
Abstract
PURPOSE: Human gene icb-1 recently has been reported to be part of a gene expression score predicting response to antiestrogen fulvestrant in breast cancer patients. In the present study, we examined to what extent icb-1 expression would affect the response of breast cancer cells to this antiestrogen in vitro and investigated underlying molecular mechanisms. Using open access mRNA data, we elucidated the significance of icb-1 expression for survival of breast cancer patients. METHODS: Icb-1 gene expression was knocked down by RNAi. Breast cancer cell growth after treatment with fulvestrant was assessed using the Cell Titer Blue assay. Gene expression was analyzed by Western blot analysis or RT-qPCR. Survival analyses were performed using bioinformatical online tools and data. RESULTS: Knockdown of icb-1 in T-47D breast cancer cells significantly increased growth of this cell line and also elevated the growth-stimulatory effect of E2 (p < 0.001). After treatment with different concentrations of fulvestrant, icb-1 knockdown cells exhibited a significantly enhanced response to this drug (p < 0.01). On the molecular level, icb-1 knockdown led to elevated expression of ESR1 and its target gene TFF1 (pS2) and enhanced E2-triggered up-regulation of proliferation genes. Finally, bioinformatical meta-analysis of gene expression data of 3951 breast cancer patients revealed that high icb-1 expression increases their relapse-free survival (HR = 0.87, p < 0.05). CONCLUSION: The presented data further support a tumor-suppressive role of icb-1 in breast cancer and suggest an inhibitory effect of this gene on fulvestrant action, which both are suggested to be mediated by suppression of cellular E2 response.
PURPOSE:Human gene icb-1 recently has been reported to be part of a gene expression score predicting response to antiestrogen fulvestrant in breast cancerpatients. In the present study, we examined to what extent icb-1 expression would affect the response of breast cancer cells to this antiestrogen in vitro and investigated underlying molecular mechanisms. Using open access mRNA data, we elucidated the significance of icb-1 expression for survival of breast cancerpatients. METHODS: Icb-1 gene expression was knocked down by RNAi. Breast cancer cell growth after treatment with fulvestrant was assessed using the Cell Titer Blue assay. Gene expression was analyzed by Western blot analysis or RT-qPCR. Survival analyses were performed using bioinformatical online tools and data. RESULTS: Knockdown of icb-1 in T-47D breast cancer cells significantly increased growth of this cell line and also elevated the growth-stimulatory effect of E2 (p < 0.001). After treatment with different concentrations of fulvestrant, icb-1 knockdown cells exhibited a significantly enhanced response to this drug (p < 0.01). On the molecular level, icb-1 knockdown led to elevated expression of ESR1 and its target gene TFF1 (pS2) and enhanced E2-triggered up-regulation of proliferation genes. Finally, bioinformatical meta-analysis of gene expression data of 3951 breast cancerpatients revealed that high icb-1 expression increases their relapse-free survival (HR = 0.87, p < 0.05). CONCLUSION: The presented data further support a tumor-suppressive role of icb-1 in breast cancer and suggest an inhibitory effect of this gene on fulvestrant action, which both are suggested to be mediated by suppression of cellular E2 response.
Authors: Oliver Treeck; Susanne Schüler; Julia Häring; Maciej Skrzypczak; Claus Lattrich; Olaf Ortmann Journal: Cancer Lett Date: 2013-03-06 Impact factor: 8.679
Authors: Martina Haselberger; Anette Springwald; Anna Konwisorz; Claus Lattrich; Regina Goerse; Olaf Ortmann; Oliver Treeck Journal: Int J Mol Med Date: 2011-03-31 Impact factor: 4.101
Authors: Matthew J Peirce; Matthew Brook; Nicholas Morrice; Robert Snelgrove; Shajna Begum; Alessandra Lanfrancotti; Clare Notley; Tracy Hussell; Andrew P Cope; Robin Wait Journal: PLoS One Date: 2010-07-13 Impact factor: 3.240
Authors: Anna Konwisorz; Anette Springwald; Martina Haselberger; Regina Goerse; Olaf Ortmann; Oliver Treeck Journal: Endocr Relat Cancer Date: 2010-02-18 Impact factor: 5.678