Absence of Parathyroid Hormone Messenger RNA in Nonparathyroid Tumors Associated with Hypercalcemia

• Published in: The New England journal of medicine Vol. 309; no. 6; pp. 325 - 330
• Main Authors: Simpson, Ellen L, Mundy, Gregory R, D'Souza, Sharyn M, Ibbotson, Kenneth J, Bockman, Richard, Jacobs, John W
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 11.08.1983
• Subjects: Adult; Aged; Animals; Breast cancer; Calcium; Calcium (blood); Cancer; Cells, Cultured; Cellulose; Chromatography; Cloning; Deoxyribonucleic acid; DNA; Endocrinology; Enzymes; Female; Humans; Hybridization; Hypercalcemia; Hypercalcemia - etiology; Laboratories; Male; Metabolism; Middle Aged; mRNA; Neoplasms - analysis; Neoplasms - metabolism; Nucleic Acid Hybridization; Parathyroid; Parathyroid hormone; Parathyroid Hormone - biosynthesis; Parathyroid Hormone - physiology; RNA, Messenger - analysis; Tumors
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198308113090601

We used a sensitive and specific hybridization assay that detects evidence of parathyroid hormone synthesis in tumors to investigate whether this hormone mediates the hypercalcemia of malignant disease. The assay uses Radio-labeled, cloned parathyroid hormone DNA to hybridize selectively with parathyroid hormone messenger RNA. We assayed 13 human and 3 animal tumors of diverse cell origins that are frequently associated with the hypercalcemia of cancer. Five of the human tumors were obtained from patients known to be hypercalcemic at the time of tumor excision, two were from normocalcemic patients, and six were from patients with breast cancer whose serum calcium levels were unknown. Messenger RNA was prepared from cultured cell lines or tumors; active RNA fractions were hybridized with either human or bovine cloned parathyroid hormone DNA that had been labeled to a high specific activity with [ 32 P]nucleotide. We were unable to detect parathyroid hormone RNA transcripts in any of the tumors. Our results indicate that parathyroid hormone rarely, if ever, causes hypercalcemia in malignant disease. (N Engl J Med 1983; 309: 325–30.) Hypercalcemia is frequently associated with malignant disease. Such hypercalcemia is due to an increase in bone resorption, but the pathogenesis of the increase is unknown in the majority of cases. 1 In patients with myeloma and other hematologic neoplasms, the lymphokine osteoclast-activating factor is the likely causative mediator. 2 However, hypercalcemia also occurs in patients who have solid tumors without osteolytic bone destruction. Since this type of hypercalcemia is often associated with hypophosphatemia and increased nephrogenous cyclic AMP generation, 3 which are features of excessive parathyroid hormone, the condition has been called "ectopic hyperparathyroidism" or "pseudohyperparathyroidism." The frequency of ectopic production of parathyroid . . .