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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 2 497-500
Copyright © 2001 by The Endocrine Society

Special Articles

The Autosomal Dominant Hypophosphatemic Rickets (ADHR) Gene Is a Secreted Polypeptide Overexpressed by Tumors that Cause Phosphate Wasting

Kenneth E. White, Kenneth B. Jonsson, Gwenaelle Carn, Geeta Hampson, Tim D. Spector, Michael Mannstadt, Bettina Lorenz-Depiereux, Akimitsu Miyauchi, In Myung Yang, Östen Ljunggren, Thomas Meitinger, Tim M. Strom, Harald Jüppner and Michael J. Econs

Departments of Medicine (K.E.W., G.C., M.J.E.) and Medical and Molecular Genetics (M.J.E.), Indiana University School of Medicine, Indianapolis, Indiana 46202; Endocrine Unit, Department of Medicine (K.B.J., M.M., H.J.), and MassGeneral Hospital for Children (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Chemical Pathology (G.H.) and Twin Research Unit (T.D.S.), St. Thomas’ Hospital, London, SE1 7EH, United Kingdom; Abteilung Medizinische Genetik, Klinikum Innenstadt (B.L.-D., T.M., T.M.S.), Ludwig-Maximilians-Universität, 80336 München, Germany; Department of Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, and National Sanatorium Hyogo Chuo Hospital 1314 Ohara, Sanda 669-1515, Japan (A.M.); Department of Internal Medicine (I.M.Y.), Kuyunghee University, Seoul, Korea; and Department of Medical Sciences (O.L.), University of Uppsala, Uppsala 751 85, Sweden

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".




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Home page
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Home page
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