Positive and negative control of the expression of parathyroid hormone (PTH)/PTH-related protein receptor via proximal promoter P3 in human osteoblast-like cells

Three promoters, P1, P2, and P3, regulate the expression of the receptor fo r the human PTH/PTH -related protein. The P3 promoter, proximal to the gene , seems to be turned on in many tissues and to be the most active of the th ree in the human adult kidney. P3 is also active in human osteoblastic SaOS -2 cells. Its structure to function relationship is, however, still poorly understood. To address this issue we assayed, in transiently transfected Sa OS-2 cells, the expression of reporter gene constructs containing truncated P3 promoter fragments and substitution mutants. We thus localized cis-acti ng elements essential for P3 promoter activity and identified two key Spl b inding sites. We also found in the 5'-untranslated exon U4, transcribed fro m promoter P3, an element that inhibits the expression of the receptor and is not promoter specific. This study provides new insights into PTH recepto r expression in human osteoblast-like cells.