Up-regulation of RhoB by glucocorticoids and its effects on the cell proliferation and NF-kappaB transcriptional activity.
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.
Chen
Yu-Xia
YX
Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
Li
Zong-Bin
ZB
Diao
Fei
F
Cao
Dong-Mei
DM
Fu
Chen-Chun
CC
Lu
Jian
J
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
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