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Effects of estrogen on the proportion of stem cells in the breast

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Abstract

There is increasing evidence that breast cancers contain tumor-initiating cells with stem cell properties. The importance of estrogen in the development of the mammary gland and in breast cancer is well known, but the influence of estrogen on the stem cell population has not been assessed. We show that estrogen reduces the proportion of stem cells in the normal human mammary gland and in breast cancer cells. The embryonic stem cell genes NANOG, OCT4, and SOX2 are expressed in normal breast stem cells and at higher levels in breast tumor cells and their expression decreases upon differentiation. Overexpression of each stem cell gene reduces estrogen receptor (ER) expression, and increases the number of stem cells and their capacity for invasion, properties associated with tumorigenesis and poor prognosis. These results indicate that estrogen reduces the size of the human breast stem cell pool and may provide an explanation for the better prognosis of ER-positive tumors.

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Acknowledgments

We thank the participating women for their willingness to cooperate with our study. We also thank Robert Kypta (CIC bioGUNE) for NTera2/D1 cells and critical reading of the manuscript, present and past members of the laboratory for help and discussions, and James Sutherland (CIC bioGUNE) for help and advice. This work was supported by grants from the ‘Spanish Ministry of Education and Science’, the ‘Institute of Health Carlos III’, the ‘Department of Education of the Government of the Autonomous Community of the Basque Country’, the ‘Department of Industry, Tourism and Trade’ (Etortek), and ‘Department of Innovation Technology of the Government of the Autonomous Community of the Basque Country’ to MV; ‘Foundation for Science and Technology of the Portuguese Ministry of Science, Technology and Higher Education’ to BMS; ‘Foundation La Caixa’ to MV and MP; ‘Department of Education of the Government of the Autonomous Community of the Basque Country’ to OI.

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Authors and Affiliations

  1. Cell Biology and Stem Cells Unit, CIC bioGUNE, Technological Park of Bizkaia, Ed 801A, 48160, Derio, Vizcaya, Spain

    Bruno M. Simões, Marco Piva, Oihana Iriondo, Valentine Comaills & Maria d.M. Vivanco

  2. Servicio de Radiodiagnostico Preteimagen, 48010, Bilbao, Spain

    Jose A. López-Ruiz

  3. Department of Pathology, Galdakao-Usansolo Hospital, Galdakao, Spain

    Iñaki Zabalza

  4. Gynecological Institute Deusto, Bilbao, Spain

    Jon A. Mieza

  5. Pathological Anatomy, Sierrallana Hospital, Torrelavega, Spain

    Olga Acinas

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  1. Bruno M. Simões
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Correspondence to Maria d.M. Vivanco.

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Simões, B.M., Piva, M., Iriondo, O. et al. Effects of estrogen on the proportion of stem cells in the breast. Breast Cancer Res Treat 129, 23–35 (2011). https://doi.org/10.1007/s10549-010-1169-4

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