PTH mRNA transcription analysis in infantile tumors associated with hypercalcemia

The ability of infantile hypercalcemic tumors (three rhabdoid renal tumors, one cellular mesoblastic nephroma, and one hepatoblastoma) to produce parathyroid hormone (PTH) was tested using RNA-DNA hybridization. Results were compared with those obtained in one lung epidermoid carcinoma and one parathyroid adenoma from adult patients. Elevated plasma immunoreactive PTH (iPTH) concentrations were observed in three of five children. The only tumor in which PTH-RNA hybridization could be detected was the parathyroid adenoma. The integrity of the RNA preparations was further confirmed by positive hybridization obtained with a glucagon DNA probe in both normal pancreas and the rhabdoid tumors. Quantitative bone histomorphometry of tumor-bearing nude mice showed a reduction in bone formation and increased bone resorption, the opposite of what occurs in hyperparathyroidism. The PTH-like protein, which was detected by radioimmunoassays (RIA) in the sera of three patients, could not be correlated with tumor PTH mRNA transcription within the limits of our assays. In order to explain this discrepancy, we suggest that the tumors produce a factor (not PTH) which, in turn, elicits the excess iPTH which we detected by RIA.