Parathyroid hormone/parathyroid hormone-related protein receptor expression in nude mice with a transplantable canine apocrine adenocarcinoma (CAC-8) and humoral hypercalcaemia of malignancy.
The effect of humoral hypercalcaemia of malignancy (HHM) on parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor expression was investigated in nude mice with subcutaneous transplantation of an adenocarcinoma line (CAC-8) which produces PTHrP. Serum calcium and PTHrP concentrations were analysed by colorimetric assay and a two-site IRMA respectively. Mice were hypercalcaemic (3.3 +/- 0.1 mmol/l) compared with non-tumour-bearing control mice (2.1 +/- 0.1 mmol/l) and had elevated serum PTHrP concentrations (30.4 +/- 3.4 pmol/l) compared with nontumour-bearing control mice (0.7 +/- 0.1 pmol/l). Lumbar vertebrae were analysed by histomorphometry. Tumour-bearing mice had a significant (P < 0.01) increase in resorptive perimeter, increased numbers of osteoclasts/mm endosteum and increased endosteal bone-forming perimeter. Total RNA was isolated from calvarium, humerus and kidney and analysed for PTH/PTHrP receptor expression by Northern blot analysis. There was no significant difference between PTH/PTHrP receptor mRNA expression in the kidney and humeri of tumour-bearing mice compared with non-tumour control mice, but a significant increase in PTH/PTHrP receptor expression in calvaria. Kidneys and vertebral bodies were stained for PTH/PTHrP receptor protein by immunohistochemistry. Renal proximal tubules (especially the basolateral regions) and endosteal osteoblasts of control and tumour-bearing mice stained positive for PTH/PTHrP receptor. These results demonstrated that HHM induced by increased serum PTHrP concentrations did not result in down-regulation of PTH/PTHrP receptor mRNA or protein expression in vivo.
Gröne
A
A
Department of Veterinary Biosciences, Ohio State University, Columbus, USA.
McCauley
L K
LK
Capen
C C
CC
Rosol
T J
TJ
D000230:Adenocarcinoma / Q000150:complications* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001842:Bone and Bones / Q000378:metabolism; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000150:complications* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone