Glucocorticoid receptor function possibly modulates cell-cell interactions in osteoblastic metastases on rat skeleton.
We analysed the glucocorticoid receptor (GR) function and its ability to modulate cell-cell interactions between the PA-III rat prostate cancer and UMR 106 osteoblast-like rat osteosarcoma cells as an in vitro model for studying GR function in PA-III cell-induced tumor and blastic reaction in rat bone. Intact GR was detected by ligand binding assays, DNA band-shift, and GR trans-activation analysis of PA-III and UMR 106 cells transiently transfected with the mouse mammary tumor virus thymidine kinase-chloramphenicol acetyltransferase reporter gene. Dexamethasone and transforming growth factor beta 1 (TGFbeta1) inhibited the growth of PA-III and UMR 106 cells. Dexamethasone's inhibition of PA-III and UMR 106 cells was reversed by anti-TGFbeta1 antibody and exogenous insulin-like growth factor I (IGF-I). Exogenous IGF-I, urokinase-type plasminogen activator (uPA), UMR 106 conditioned media (CM) and PA-III CM stimulated the proliferation of PA-III and UMR 106 cells. The mitogenic activity exerted by uPA and PA-III CM in UMR 106 cells was completely neutralized by anti-IGF-I specific antibody. In addition, dexamethasone up-regulated TGFbeta1 mRNA and down-regulated uPA mRNA expression in PA-III cells without affecting TGFbeta1 and uPA mRNA expression in UMR 106 cells. These data suggested that TGFbeta1, uPA, and IGF-I mediate at least in part cell-cell interactions and GR function in PA-III prostate cancer and UMR 106 osteosarcoma cells.
Reyes-Moreno
C
C
Molecular Endocrinology Laboratory, Research Center, Centre Hospitalier de L'Université Laval (C.H.U.L.), St Foy, Québec, Canada.
Koutsilieris
M
M
D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D002450:Cell Communication; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D012516:Osteosarcoma / Q000473:pathology* / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000494:pharmacology
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D004247:DNA; D014568:Urokinase-Type Plasminogen Activator