Mediation of glucocorticoid receptor function by the activation of latent transforming growth factor beta 1 in MG-63 human osteosarcoma cells.
We analyzed glucocorticoid receptor function using ligand binding assays, DNA band-shift analysis and trans-activation of the murine mammary tumor virus-thymidine kinase-chloramphenicol acetyltransferase reporter gene in transiently transfected MG-63 human osteosarcoma cells. Dexamethasone increased the distribution of MG-63 cells in the G1/G0 phase of the cell cycle, thus decreasing the rate of DNA synthesis and cell growth. Its effect on MG-63 cell growth was neutralized by RU486 and anti-transforming growth factor beta 1 (TGF beta 1) antibody. In addition, (i) dexamethasone increased the levels of active TGF beta 1 in MG-63-conditioned media without significantly altering the expression of TGF beta 1 mRNA in MG-63 cells and (ii) TGF beta 1 inhibited proliferation of MG-63 cells. Therefore, we conclude that glucocorticoid receptor function is mediated by the activation of latent-TGF beta 1 in MG-63 osteosarcoma cells.
Boulanger
J
J
Molecular Endocrinology, Research Center, Centre Hospitalier de l'Université Laval, St. Foy, Québec, Canada.
Reyes-Moreno
C
C
Koutsilieris
M
M
D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle; D002455:Cell Division; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011965:Receptors, Glucocorticoid; D016212:Transforming Growth Factor beta; D003907:Dexamethasone