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 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.
Axiotis
C A
CA
Department of Pathology, State University of New York Health Science Center at Brooklyn, Kings County Hospital Center, Brooklyn 11203.
Bani
D
D
Bianchi
S
S
Pioli
P
P
Tanini
A
A
Brandi
M L
ML
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018432:Drug Resistance, Multiple / Q000235:genetics; D004727:Endothelium / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D010280:Parathyroid Glands / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D002118:Calcium