P-GLYCOPROTEIN IS EXPRESSED IN PARATHYROID EPITHELIUM AND IS REGULATED BY CALCIUM

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 physio logic 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, parath yroid adenoma, and parathyroid carcinoma for expression of the multidr ug resistance gene (Mdr1) and Pgp utilizing Northern and Western analy sis and immunohistochemistry. We also investigated the effect of extra cellular calcium (eCa) on Pgp expression in PT-r cells at the molecula r/cellular level. Immunohistochemistry, utilizing three murine monoclo nal 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 w eak immunostaining in parathyroid adenomas. BPE-1 cells, endothelial c ells, and parathyroid carcinoma were negative. PT-r cells showed a sin gle 130 kDa band (120 KDa after glycosidase treatment) on Western blot and a 4.6 kb transcript on Northern analysis, consistent with Pgp. We stern and Northern blot analysis of PTr cells cultured in different eC a concentrations showed that eCa up-regulated Pgp expression. Northern analysis of doxorubicin-resistant human breast carcinoma cells (Adr(r )) (MCF-7) exhibited constitutive expression of Pgp mRNA without modif ications, with increasing eCa concentrations. We conclude that N-glyco sylated Pgp is expressed in parathyroid epithelial cells and that calc ium responsiveness of Pgp expression appears cell specific.