title: Proliferative effect of parathyroid hormone-related protein on the hypercalcemic Walker 256 carcinoma cell line.
abstract: The rat Walker 256 carcinoma is an animal model for humoral hypercalcemia of malignancy. This tumor produces and secretes parathyroid hormone (PTH)-related protein (PTHrP), a likely mediator for this syndrome. In this study, we investigated the effect of PTHrP on Walker 256 tumor cell proliferation. We found that [Tyr36]human (h)PTHrP (1-36)NH2 and hPTHrP (1-86), unlike hPTHrP (38-64)NH2, stimulate DNA synthesis dose-dependently in these cells. A similar mitogenic effect was also observed with bovine (b)PTH (1-34) or (Nle8.18, Tyr34)bPTH (3-34)NH2. Moreover, addition of anti-hPTHrP (1-34) neutralizing antibodies decreased tumor cell growth. Conversely, 10(-4)M dibutyryl cAMP or Sp-cDBIMPS (a cAMP analogue) inhibited DNA synthesis in these cells, being incompetent at lower doses. PTHrP or PTH failed to stimulate cAMP production, but they induced a cytosolic calcium transient increase in these cells. These findings support an autocrine role of PTHrP in the regulation of this tumor growth.
authors.affiliation: Laboratorio de la Unidad Metabólica, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Benítez-Verguizas
authors.forename: P
authors.initials: P
authors.lastname: Esbrit
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D003620:Dantrolene / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006934:Hypercalcemia / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019379:Teriparatide; D013873:Thionucleotides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D004273:DNA, Neoplasm; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D013873:Thionucleotides; C079957:parathyroid hormone-related peptide (1-36); D019379:Teriparatide; C071644:5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-monophosphorothioate; D004004:Dichlororibofuranosylbenzimidazole; D003994:Bucladesine; D000262:Adenylyl Cyclases; D003620:Dantrolene; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D013936:Thymidine