MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.
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.
Rowe
P S
PS
Centre for Molecular Osteo-Renal Research, Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Hampstead, London, United Kingdom. p.rowe@rfc.ucl.ac.uk
de Zoysa
P A
PA
Dong
R
R
Wang
H R
HR
White
K E
KE
Econs
M J
MJ
Oudet
C L
CL
D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D003198:Computer Simulation; D017077:Culture Media, Conditioned; D017931:DNA Primers / Q000737:chemistry; D003937:Diagnosis, Differential; D016326:Extracellular Matrix Proteins; D005260:Female; D015723:Gene Library; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006393:Hemangiopericytoma / Q000150:complications / Q000235:genetics; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010018:Osteomalacia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000235:genetics; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C486579:MEPE protein, human; D010455:Peptides; D010750:Phosphoproteins; D012333:RNA, Messenger