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Icb-1 expression inhibits growth and fulvestrant response of breast cancer cells and affects survival of breast cancer patients

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

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.

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Data availability

Data and materials are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Mrs. Bettina Federhofer for expert technical assistance.

Funding

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany

    Maria Riedmeier, Susanne Schüler-Toprak, Olaf Ortmann & Oliver Treeck

  2. Second Department of Gynecology, Medical University of Lublin, Lublin, Poland

    Maciej Skrzypczak

Authors
  1. Maria Riedmeier
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  2. Maciej Skrzypczak
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  3. Susanne Schüler-Toprak
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  4. Olaf Ortmann
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  5. Oliver Treeck
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Contributions

MR: data collection and management, and data analysis. MS, SS: data analysis and manuscript editing. OO: providing essential project support and manuscript editing. OT: protocol/project development, data collection and management, data analysis, and manuscript writing/editing.

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Correspondence to Oliver Treeck.

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All authors state that they do not have any conflicts of interest with regard to this study.

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Riedmeier, M., Skrzypczak, M., Schüler-Toprak, S. et al. Icb-1 expression inhibits growth and fulvestrant response of breast cancer cells and affects survival of breast cancer patients. Arch Gynecol Obstet 304, 203–213 (2021). https://doi.org/10.1007/s00404-020-05902-x

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  • DOI: https://doi.org/10.1007/s00404-020-05902-x

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