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Expression of sigma 1 receptor in human breast cancer

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Abstract

The sigma 1 receptor (S1R) represents a unique drug-binding site that is distinct from any other receptors. We examined S1R expression in human breast cancer and assessed the activity of S1R ligands in breast cancer cell lines. One-hundred nine breast specimens from normal breast, benign breast disease and cancer were examined with immunohistochemistry or RT- PCR and six different cell lines were also evaluated. S1R mRNA overexpression was detected in 64% of breast cancers compared to normal breast tissue. Immunohistochemistry showed positive epithelial cell staining in 60% of invasive and 41% of in situ cancers, 75% of ductal hyperplasia and in 33% of normal breast. The pattern of expression was more diffuse in invasive breast carcinoma compared to other conditions (p = 0.02). S1R expression was neither a prognostic nor a predictive factor for efficacy of adjuvant chemotherapy but the study only included 58 cancer patients and therefore the statistical power is limited. MDA - MB −361, MDA - MB −435, BT 20 and MCF 7 cells all expressed S1R protein by Western blot. The non-specific S1R ligands haloperidol, reduced haloperidol and progesterone produced a dose-dependent inhibition of the growth at high (>10 μM) concentrations. Reduced haloperidol also showed additive cytotoxic effects when combined with doxorubicin, vinorelbine , paclitaxel and docetaxel in vitro. The S1R-specific ligand, SKF 10047 demonstrated the least growth inhibitory activity and showed no interaction with chemotherapy. These results demonstrate that some normal and most neoplastic breast epithelial cells and cell lines commonly express S1R. High concentrations of haloperidol inhibit the growth of these cells and potentiate the effect of chemotherapy in vitro.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD, Anderson Cancer Center, 1515 Holcombe Boulevard, TX, USA

    B. Wang, R. Rouzier, P. Wagner, F. Meric Bernstam, G. N. Hortobagyi & L. Pusztai

  2. Department of Breast Cancer Research Program Core Laboratory, The University of Texas MD Anderson Cancer Center, TX, USA

    B. Wang, R. Rouzier, P. Wagner, F. Meric Bernstam & L. Pusztai

  3. Department of Pathology, The University of Texas MD Anderson Cancer Center, TX, USA

    C. T. Albarracin & A. Sahin

  4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, TX, USA

    Y. Yang & T. L. Smith

  5. Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, TX, USA

    A. C. Marcelo

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  1. B. Wang
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  2. R. Rouzier
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  3. C. T. Albarracin
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  4. A. Sahin
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  5. P. Wagner
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  6. Y. Yang
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  7. T. L. Smith
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  8. F. Meric Bernstam
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  9. A. C. Marcelo
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  10. G. N. Hortobagyi
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  11. L. Pusztai
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Wang, B., Rouzier, R., Albarracin, C.T. et al. Expression of sigma 1 receptor in human breast cancer. Breast Cancer Res Treat 87, 205–214 (2004). https://doi.org/10.1007/s10549-004-6590-0

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  • DOI: https://doi.org/10.1007/s10549-004-6590-0

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