title: Up-regulation of RhoB by glucocorticoids and its effects on the cell proliferation and NF-kappaB transcriptional activity.
abstract: Although there is ample evidence that glucocorticoids (GCs) have an antiproliferative effect on many cell types, the molecular mechanism remains elusive. We reported in our previous study that Dex treatment led to cell growth arrest in a human ovarian cancer cell HO-8910. RhoB, as a member of Rho GTPases, have been implicated to be a negative regulator of cell proliferation. In this study, we provided novel evidence that Dex induced the expressions of small GTPase RhoB mRNA and protein, but not RhoA and RhoC mRNA in a dose- and time-dependent fashion via glucocorticoid receptor (GR). Over-expression of RhoB increased while inhibition of RhoB expression by RNA interference reversed Dex-induced growth arrest, indicating that RhoB signaling is involved in Dex-induced proliferation inhibition. We also presented the novel observation that over-expression or activation of RhoB signaling elevated the basal transcriptional activity of the transcription factor NF-kappaB in HO-8910 cells. Furthermore, elevating RhoB signaling enhanced the inhibitory effect of Dex on NF-kappaB activity, while attenuating RhoB signaling almost abrogated Dex suppression of NF-kappaB signaling, indicating that RhoB pathway is involved in the regulation of NF-kappaB activity and is essential for Dex transcriptional repression on NF-kappaB signaling in HO-8910 cells.
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Chen
authors.forename: Zong-Bin
authors.initials: ZB
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Diao
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Cao
authors.forename: Chen-Chun
authors.initials: CC
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein