SEQUENCE AND ACTIVITY OF PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PROTEIN-RECEPTOR PROMOTER REGION IN HUMAN OSTEOBLAST-LIKE CELLS

The parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor gen e has been characterized in various species. The structure of its prom oter and the regulation of its expression in human tissues have, howev er, not been clearly established yet. We characterized the region upst ream of the PTH/PTHrP receptor gene and investigated its promoter acti vity in the human osteoblastlike SaOS-2 cells. In this region, three u ntranslated exons were localized, U1 and U2 by using a kidney cDNA, an d U3 by homology with the mouse gene. In human osteoblast-like cells, a distal promoter(P1) was found to be inactive, as evaluated by lucife rase reporter gene assays, in contrast to the situation found in human and mouse kidney tissue. A second promoter (P2), previously described in mouse and human kidney, was shown to be active in human osteoblast -like SaOS-2 cells. We found a hitherto uncharacterized promoter (P3), closely upstream of the ATG start codon. The activities of P2 and P3 were not additive. These results provide important information on the structure of the 5' flanking region of the human PTH/PTHrP gene recept or. (C) 1998 Elsevier Science B.V. All rights reserved.