title: Two forms of parathyroid hormone-like adenylate cyclase-stimulating protein derived from tumors associated with humoral hypercalcemia of malignancy.
abstract: Tumors associated with humoral hypercalcemia of malignancy (HHM) contain parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs). We previously purified a 17,000 MW hACSP from an HHM-associated breast carcinoma. This report describes the characterization of hACSPs from three additional HHM-associated tumors: two typical HHM-associated tumors (squamous carcinomas) and a third unusual tumor type (pheochromocytoma). Each tumor was extracted in acid-urea/ethanol-sodium chloride, and adenylate cyclase-stimulating activity (ACSA) was examined following reverse-phase and size-exclusion HPLC and isoelectric focusing. Each tumor contained a high molecular weight form of ACSA which co-eluted with the 17,000 molecular weight breast carcinoma hACSP in each of the three separation procedures. Each also contained a lower molecular weight form(s) of ACSA (6,000-9,000 molecular weight). Both forms were inhibited by Nle8,18Tyr34bPTH(3-34) amide. The high molecular weight form was not changed to the lower molecular weight form by a reducing agent. Some HHM-associated tumors contain two forms of hACSP, one with a molecular weight of 17,000 and another with a molecular weight of 6,000-9,000, which appears to be an amino-terminal cleavage product of the larger protein.
authors.affiliation: Division of Endocrinology, West Haven VA Medical Center, CT 06516.
authors.forename: A F
authors.initials: AF
authors.lastname: Stewart
authors.forename: W J
authors.initials: WJ
authors.lastname: Burtis
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.forename: D
authors.initials: D
authors.lastname: Goumas
authors.forename: A E
authors.initials: AE
authors.lastname: Broadus
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000368:Aged; D000818:Animals; D001681:Biological Assay; D001943:Breast Neoplasms / Q000032:analysis / Q000150:complications; D002294:Carcinoma, Squamous Cell / Q000032:analysis*; D004285:Dogs; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000032:analysis / Q000150:complications; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis* / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000032:analysis*; D012878:Skin Neoplasms / Q000032:analysis / Q000150:complications
chemical_list: D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D000262:Adenylyl Cyclases