Regulation of the transcription of parathyroid-hormone/parathyroid-hormone-related peptide receptor mRNA by dexamethasone in ROS 17/2.8 osteosarcoma cells.
Previous studies have shown that dexamethasone enhanced the expression of parathyroid-hormone/parathyroid-hormone-related peptide (PTH/ PTHrP) receptor mRNA in ROS 17/2.8 osteosarcoma cells. The aim of this study was to determine whether the induction of PTH/PTHrP receptor expression in such osteoblast-like cells is regulated at the gene level. Dexamethasone increased the steady-state levels of PTH/PTHrP receptor mRNA twofold at 6 h, and nearly threefold at 24 h. The half-life of the PTH/PTHrP receptor mRNA, in the presence of actinomycin D, was 6 h both in untreated and in dexamethasone-treated cells. When measured by nuclear run-on assay, the rate of PTH/PTHrP receptor gene transcription was increased twofold at 24 h. PTH/PTHrP receptor mRNA expression was blocked completely after 24 h of treatment with cycloheximide. The binding of PTH/PTHrP to their receptor required the synthesis of new protein and was shown to be specifically dependent on the interaction of dexamethasone with the glucocorticoid receptor. These data indicate that the enhancing effect of dexamethasone on PTH/PTHrP receptor expression is rapid, requires de novo protein synthesis, and increases the transcription rate of the PTH/PTHrP receptor gene.
Yaghoobian
J
J
INSERM Unité 90, Hôpital Necker, Paris, France.
Drüeke
T B
TB
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001859:Bone Neoplasms; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D006207:Half-Life; D012516:Osteosarcoma / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018016:Receptors, Parathyroid Hormone / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D044162:Parathyroid Hormone-Related Protein; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide