The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting

Kenneth White, K. B. Jonsson, G. Carn, G. Hampson, T. D. Spector, M. Mannstadt, B. Lorenz-Depiereux, A. Miyauchi, Myung Yang In Myung Yang, O. Ljunggren, T. Meitinger, T. M. Strom, H. Jüppner, Michael Econs

Research output: Contribution to journalArticle

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Abstract

The gene mutated in autosomal dominant hypophosphatemic rickets (ADHR), a phosphate wasting disorder, has been identified as FGF-23, a protein that shares sequence homology with fibroblast growth factors (FGFs). Patients with ADHR display many of the clinical and laboratory characteristics that are observed in patients with oncogenic hypophosphatemic osteomalacia (OHO), a disorder thought to arise by the secretion of a phosphate wasting factor from different mesenchymal tumors. In the present studies, we therefore investigated whether FGF-23 is a secreted factor and whether it is abundantly expressed in OHO tumors. After transient transfection of OK-E, COS-7, and HEK293 cells with the plasmid encoding full-length FGF-23, all three cell lines efficiently secreted two protein species into the medium that were approximately 32 and 12 kDa upon SDS-PAGE and subsequent Western blot analysis using an affinity-purified polyclonal antibody to FGF-23. Furthermore, Northern blot analysis using total RNA from five different OHO tumors revealed extremely high levels of FGF-23 mRNA, and Western blot analysis of extracts from a sixth tumor detected the 32 kDa FGF-23 protein species. In summary, FGF-23, the gene mutated in ADHR, is a secreted protein and its mRNA is abundantly expressed by several different OHO tumors. Our findings indicate that FGF-23 may be a candidate phosphate wasting factor, previously designated "phosphatonin".

Original languageEnglish
Pages (from-to)497-500
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number2
DOIs
StatePublished - 2001

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Tumors
Genes
Phosphates
Peptides
Neoplasms
Proteins
Western Blotting
Amino Acid Sequence Homology
Messenger RNA
Fibroblast Growth Factors
fibroblast growth factor 23
Autosomal Dominant Hypophosphatemic Rickets
HEK293 Cells
COS Cells
Northern Blotting
Transfection
Polyacrylamide Gel Electrophoresis
Plasmids
Cells
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. / White, Kenneth; Jonsson, K. B.; Carn, G.; Hampson, G.; Spector, T. D.; Mannstadt, M.; Lorenz-Depiereux, B.; Miyauchi, A.; In Myung Yang, Myung Yang; Ljunggren, O.; Meitinger, T.; Strom, T. M.; Jüppner, H.; Econs, Michael.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 2, 2001, p. 497-500.

Research output: Contribution to journalArticle

White, K, Jonsson, KB, Carn, G, Hampson, G, Spector, TD, Mannstadt, M, Lorenz-Depiereux, B, Miyauchi, A, In Myung Yang, MY, Ljunggren, O, Meitinger, T, Strom, TM, Jüppner, H & Econs, M 2001, 'The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting', Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 2, pp. 497-500. https://doi.org/10.1210/jc.86.2.497
White, Kenneth ; Jonsson, K. B. ; Carn, G. ; Hampson, G. ; Spector, T. D. ; Mannstadt, M. ; Lorenz-Depiereux, B. ; Miyauchi, A. ; In Myung Yang, Myung Yang ; Ljunggren, O. ; Meitinger, T. ; Strom, T. M. ; Jüppner, H. ; Econs, Michael. / The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 2. pp. 497-500.
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