CO-PURIFICATION OF TRANSFORMING GROWTH FACTOR LIKE ACTIVITY WITH PTH-LIKE AND BONE-RESORBING ACTIVITIES FROM A TUMOR ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY
1987; Oxford University Press; Volume: 120; Issue: 5 Linguagem: Inglês
10.1210/endo-120-5-2183
ISSN1945-7170
AutoresKarl Insogna, Eleanor C. Weir, Terence Wu, Andrew F. Stewart, Arthur E. Broadus, William J. Burtis, Michael Centrella,
Tópico(s)Erythrocyte Function and Pathophysiology
ResumoHumoral hypercalcemia of malignancy (HHM) is caused by a circulating bone-resorbing factor or factors. Suggestions as to the nature of this factor include PTH-like proteins, transforming growth factors, and bone-resorbing factors distinct from either of the first two classes of polypeptides. We investigated the occurrence of these three activities in a highly purified extract of the H-500 Leydig cell tumor which causes HHM when implanted into Fisher rats. PTH-like adenylate cyclase-stimulating activity (ACSA) was extracted from tumor tissue by sequential treatment with urea/HCl and ethanol/NaCl. Tumor extract was further purified by hydrophobic-interaction, gel-filtration, and reverse-phase HPLC steps to a specific activity of 1038 ng eq bPTH(l–34)/mg protein. Only the fraction pool containing ACSA demonstrated significant bone-resorbing (1.78-fold over basal) and transforming growth factor activity (epidermal growth factor (EGF)-dependent colony formation in soft agar suspension by NRK-49F indicator cells). A subsequent reverse-phase HPLC step produced material which contained both ACSA and transforming growth factor beta (TGF β)-like activity in a single fraction. Whether the responsible mediator in this animal model has TGF β-like properties as well as PTH-like and bone-resorbing activity remains to be determined.
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