MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia

Peter S N Rowe, Priyal A. De Zoysa, Rong Dong, Huei Rong Wang, Kenneth White, Michael Econs, Claudine L. Oudet

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Abstract

Oncogenic hypophosphatemic osteomalacia (OHO) is characterized by a renal phosphate leak, hypophosphatemia, low-serum calcitriol (1,25-vitamin- D3), and abnormalities in skeletal mineralization. Resection of OHO tumors results in remission of the symptoms, and there is evidence that a circulating phosphaturic factor plays a role in the bone disease. This paper describes the characterization and cloning of a gene that is a candidate for the tumor-secreted phosphaturic factor. This new gene has been named MEPE (matrix extracellular phosphoglycoprotein) and has major similarities to a group of bone-tooth mineral matrix phospho-glycoproteins (osteopontin (OPN; HGMW-approved symbol SPP1), dentin sialo phosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein II (IBSP), and bone morphogenetic proteins (BMP). All the proteins including MEPE contain RGD sequence motifs that are proposed to be essential for integrin-receptor interactions. Of further interest is the finding that MEPE, OPN, DSPP, DMP1, IBSP, and BMP3 all map to a defined region in chromosome 4q. Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and D4S2844 (WI-3770). MEPE is 525 residues in length with a short N-terminal signal peptide. High-level expression of MEPE mRNA occurred in all four OHO tumors screened. Three of 11 non-OHO tumors screened contained trace levels of MEPE expression (detected only after RT-PCR and Southern 32P analysis). Normal tissue expression was found in bone marrow and brain with very-low-level expression found in lung, kidney, and human placenta. Evidence is also presented for the tumor secretion of clusterin (HGMW-approved symbol CLU) and its possible role as a cytotoxic factor in one of the OHO patients described. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)54-68
Number of pages15
JournalGenomics
Volume67
Issue number1
DOIs
StatePublished - Jul 1 2000

Fingerprint

Osteomalacia
Extracellular Matrix
Bone Marrow
Genes
Neoplasms
Dentin
Integrin-Binding Sialoprotein
Clusterin
Hypophosphatemia
Kidney
Bone Morphogenetic Proteins
Osteopontin
Calcitriol
Cholecalciferol
Extracellular Matrix Proteins
Bone Diseases
Expressed Sequence Tags
Protein Sorting Signals
Integrins
Placenta

ASJC Scopus subject areas

  • Genetics

Cite this

Rowe, P. S. N., De Zoysa, P. A., Dong, R., Wang, H. R., White, K., Econs, M., & Oudet, C. L. (2000). MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Genomics, 67(1), 54-68. https://doi.org/10.1006/geno.2000.6235

MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. / Rowe, Peter S N; De Zoysa, Priyal A.; Dong, Rong; Wang, Huei Rong; White, Kenneth; Econs, Michael; Oudet, Claudine L.

In: Genomics, Vol. 67, No. 1, 01.07.2000, p. 54-68.

Research output: Contribution to journalArticle

Rowe, PSN, De Zoysa, PA, Dong, R, Wang, HR, White, K, Econs, M & Oudet, CL 2000, 'MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia', Genomics, vol. 67, no. 1, pp. 54-68. https://doi.org/10.1006/geno.2000.6235
Rowe, Peter S N ; De Zoysa, Priyal A. ; Dong, Rong ; Wang, Huei Rong ; White, Kenneth ; Econs, Michael ; Oudet, Claudine L. / MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. In: Genomics. 2000 ; Vol. 67, No. 1. pp. 54-68.
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