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P-glycoprotein is expressed in parathyroid epithelium and is regulated by calcium

  • Molecular and Cellular Biology
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Abstract

P-glycoprotein (Pgp), the multidrug resistance (mdr) gene product, has been described in normal tissues with diverse physiologic functions. A broad role as a transporter protein for toxins, hormones, and physiologic metabolites has been provisionally deduced, based on structural analysis and immunoanatomic localization. Recently, significant levels of Pgp have been demonstrated in endocrine and hormonally responsive tissues and tumors. We examined calcium-regulated, clonal parathyroid epithelial (PT-r) and endothelial cells (BPE-1) and frozen parathyroid tissue from normal human parathyroid, parathyroid hyperplasia, parathyroid adenoma, and parathyroid carcinoma for expression of the multidrug resistance gene (Mdr1) and Pgp utilizing Northern and Western analysis and immunohistochemistry. We also investigated the effect of extracellular calcium (eCa) on Pgp expression in PT-r cells at the molecular/cellular level. Immunohistochemistry, utilizing three murine monoclonal antibodies (MAbs)—C494, JSB-1, and C219—which recognize spatially distinct cytoplasmic epitopes of Pgp, revealed strong immunoreactivity in PT-r cells, normal parathyroid, and parathyroid hyperplasia, and weak immunostaining in parathyroid adenomas. BPE-1 cells, endothelial cells, and parathyroid carcinoma were negative. PT-r cells showed a single 130 kDa band (120 KDa after glycosidase treatment) on Western blot and a 4.6 kb transcript on Northern analysis, consistent with Pgp. Western and Northern blot analysis of PTr cells cultured in different eCa concentrations showed that eCa up-regulated Pgp expression. Northern analysis of doxorubicin-resistant human breast carcinoma cells (Adr1) (MCF-7) exhibited constitutive expression of Pgp mRNA without modifications, with increasing eCa concentrations. We conclude that N-glycosylated Pgp is expressed in parathyroid epithelial cells and that calcium responsiveness of Pgp expression appears cell specific.

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Authors and Affiliations

  1. Department of Pathology, State University of New York Health Science Center at Brooklyn, Kings County Hospital Center, 450 Clarkson Avenue, Box 25, 11203, Brooklyn, New York

    C. A. Axiotis

  2. Department of Human Anatomy and Histology, Section of Histology, University of Florence Medical School, Florence, Italy

    D. Bani

  3. Endocrine Unit, Department of Clinical Physiopathology, University of Florence Medical School, Florence, Italy

    S. Bianchi, P. Pioli, A. Tanini & M. L. Brandi

Authors
  1. C. A. Axiotis
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  2. D. Bani
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  3. S. Bianchi
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  4. P. Pioli
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  5. A. Tanini
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  6. M. L. Brandi
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Axiotis, C.A., Bani, D., Bianchi, S. et al. P-glycoprotein is expressed in parathyroid epithelium and is regulated by calcium. Calcif Tissue Int 56, 170–174 (1995). https://doi.org/10.1007/BF00296351

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  • DOI: https://doi.org/10.1007/BF00296351

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