PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PROTEIN-RECEPTOR EXPRESSION IN NUDE-MICE WITH A TRANSPLANTABLE CANINE APOCRINE ADENOCARCINOMA (CAC-8) AND HUMORAL HYPERCALCEMIA OF MALIGNANCY

The effect of humoral hypercalcaemia of malignancy (HHM) on parathyroi d hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor exp ression was investigated in nude mice with subcutaneous transplantatio n of an adenocarcinoma line (CAC-8) which produces PTHrP. Serum calciu m and PTHrP concentrations were analysed by colorimetric assay and a t wo-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) comp ared with non-tumour-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 num bers of osteoclasts/mm endosteum and increased endosteal bone-forming perimeter. Total RNA was isolated from calvarium, humerus and kidney a nd analysed for PTH/PTHrP receptor expression by Northern blot analysi s. There was no significant difference between PTH/PTHrP receptor mRNA expression in the kidneys 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 sta ined for PTH/PTHrP receptor protein by immunohistochemistry. Renal pro ximal tubules (especially the basolateral regions) and endosteal osteo blasts of control and tumour-bearing mice stained positive for PTH/PTH rP receptor. These results demonstrated that HHM induced by increased serum PTHrP concentrations did not result in down-regulation of PTH/PT HrP receptor mRNA or protein expression in vivo.