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 gene has been characterized in various species. The structure of its promoter and the regulation of its expression in human tissues have, however, not been clearly established yet. We characterized the region upstream of the PTH/PTHrP receptor gene and investigated its promoter activity in the human osteoblast-like SaOS-2 cells. In this region, three untranslated exons were localized, U1 and U2 by using a kidney cDNA, and U3 by homology with the mouse gene. In human osteoblast-like cells, a distal promoter (P1) was found to be inactive, as evaluated by luciferase 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 receptor.