Decreased expression of caveolin-1 and altered regulation of mitogen-activated protein kinase in cultured bovine parathyroid cells and human parathyroid adenomas.
Caveolins are key components of caveolae membranes. The calcium-sensing receptor (CaR) resides within caveolin-rich membrane domains in bovine parathyroid (PT) cells. Recent studies reported reduced CaR expression, and abnormal calcium-sensing in PT tumors. To examine this altered CaR signaling, we investigated ERK activation after CaR stimulation in human and bovine PT cells. In freshly prepared bovine PT cells, high extracellular calcium (Ca(2+)(0)) stimulates ERK1/2 phosphorylation, and activated ERK1/2 colocalizes with caveolin-1 at the plasma membrane but fails to translocate to the nucleus, and cell proliferation is low. In cultured bovine PT cells, CaR and caveolin-1 levels are reduced; activated ERK1/2 localizes in the cell periphery at 10 min and in the perinuclear and nuclear regions at 60 min after exposure to high Ca(2+)(0), and cell proliferation is increased. In PT cells from adenomas, there are high levels of caveolin-2, variably reduced caveolin-1, and hyperactivation of ERK1/2, which colocalizes with caveolin-1 in some cells, but localizes in the cytosol and nucleus in others. Finally, caveolin-1 negative human PT cells exhibit reduced suppressibility of PTH secretion by high Ca(2+)(0). Thus, CaR and caveolin-1 colocalize in PT cells, and reduced levels of caveolin-1 could participate in the abnormal cellular function and proliferation of cultured bovine PT cells and PT adenomas.
Kifor
Olga
O
Endocrine-Hypertension Division and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. okifor@rics.bwh.harvard.edu
Kifor
Imre
I
Moore
Francis D
FD
Butters
Robert R
RR
Cantor
Thomas
T
Gao
Ping
P
Brown
Edward M
EM
D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D020013:Calcium Signaling / Q000502:physiology; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine