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STEAP1 is over-expressed in breast cancer and down-regulated by 17β-estradiol in MCF-7 cells and in the rat mammary gland

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Abstract

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) was identified as a prostate-specific cell-surface antigen over-expressed in prostate cancer, and in human cancer cell lines obtained from several other tissues. Its cell surface location in all tumor types analyzed so far, and its absence in most vital organs in humans, turned STEAP1 into a potential target for anti-tumor immunotherapy. This study provides experimental evidence that STEAP1 is also over-expressed in human breast cancer cases, and in normal breast tissue adjacent to breast tumors, where it is localized in the cell membrane of epithelial cells. It is also demonstrated that STEAP1 transcription correlates negatively with estrogen receptor (ER) immunoreactivity, and positively with tumor grading in breast cancer cases. As estrogens are involved in breast cancer onset and progression, the response of STEAP1 to 17β-estradiol (E2) was investigated in the mammary gland of rats, and in the human breast cancer cell line, MCF-7. These experiments demonstrated that STEAP1 is down-regulated by E2 in both models. The mechanisms underlying the STEAP1 response to E2 in vitro were further investigated in MCF-7 cells, and the results obtained suggest an effect mediated by the membrane-bound ERα (mbERα).

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Acknowledgments

Maia CJB is recipient of a fellowship from the Portuguese Foundation for Science and Technology-FCT, SFRH/BD/13388/2003. All the experimental work was supported by the FCT plurianual program. We acknowledge Dr. Eugenio Serrano de Dios from the University Hospital of Salamanca and Centro Hospitalar da Cova da Beira for providing breast cancer samples, Catarina Ferreira for the preparation of tissue sections, and Dr. Graça Baltazar and Telma Quintela for counselling in fluorescence microscopy.

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Authors and Affiliations

  1. Centre of Investigation in Health Sciences—CICS, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal

    Cláudio J. B. Maia, Sílvia Socorro & Cecília R. A. Santos

  2. IPATIMUP—Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

    Fernando Schmitt

  3. Medical Faculty of Porto University, Porto, Portugal

    Fernando Schmitt

Authors
  1. Cláudio J. B. Maia
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  2. Sílvia Socorro
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  3. Fernando Schmitt
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  4. Cecília R. A. Santos
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Correspondence to Cecília R. A. Santos.

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Maia, C.J.B., Socorro, S., Schmitt, F. et al. STEAP1 is over-expressed in breast cancer and down-regulated by 17β-estradiol in MCF-7 cells and in the rat mammary gland. Endocr 34, 108–116 (2008). https://doi.org/10.1007/s12020-008-9113-7

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  • DOI: https://doi.org/10.1007/s12020-008-9113-7

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