Phosphate wasting in oncogenic osteomalacia: phex is normal and the tumor-derived factor has unique properties

Oncogenic osteomalacia (OOM) is characterized by renal phosphate wasting and abnormal metabolism of vitamin D, somewhat similar to the phenotype of X-linked hypophosphatemic rickets (HYP). DNA from OOM tumor cells was analyzed for mutations in the PHEX gene, which is mutated in HYP. Screening for mu...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2001-04, Vol.28 (4), p.430-439
Main Authors: Nelson, A.E, Hogan, J.J, Holm, I.A, Robinson, B.G, Mason, R.S
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Carrier Proteins - genetics
Colchicine - pharmacology
Cotransport
Culture Media, Conditioned
Cycloheximide - pharmacology
Cytochalasin D - pharmacology
Diseases of the osteoarticular system
Humans
Hypophosphatemia
Kidney - metabolism
Medical sciences
Mutation
Oncogenic
Osteomalacia
Osteomalacia - genetics
Osteomalacia - metabolism
Osteoporosis. Osteomalacia. Paget disease
PHEX
Phex gene
PHEX Phosphate Regulating Neutral Endopeptidase
Phosphates - metabolism
Proteins - genetics
Proteins - metabolism
RNA, Messenger - genetics
Sodium-Phosphate Cotransporter Proteins
Sodium-Phosphate Cotransporter Proteins, Type II
Sodium/phosphate
Symporters
Tumor Cells, Cultured
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Summary:Oncogenic osteomalacia (OOM) is characterized by renal phosphate wasting and abnormal metabolism of vitamin D, somewhat similar to the phenotype of X-linked hypophosphatemic rickets (HYP). DNA from OOM tumor cells was analyzed for mutations in the PHEX gene, which is mutated in HYP. Screening for mutations by single-strand conformation polymorphism analysis and subsequent sequencing of all the exons revealed no mutations. Conditioned media from long-term cultures of OOM tumor cells were used to further characterize the physical properties of the phosphate-regulating factor and its mechanism of action. Inhibition of OK 3B2 cell renal phosphate transport by conditioned media was dose-dependent and maximal after 20 h. This time course differed from that of parathyroid hormone (PTH). The bioactivity was stable to mild acid and alkali treatment and freeze drying and was retained in the aqueous phase following organic solvent extraction. The activity was not suppressed by heat or by treatment with trypsin but was suppressed by the protease papain and had an apparent molecular weight of
ISSN:8756-3282
1873-2763
DOI:10.1016/S8756-3282(01)00417-3