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Over-expression of ERT(ESX/ESE-1/ELF3), an ets-related transcription factor, induces endogenous TGF-beta type II receptor expression and restores the TGF-beta signaling pathway in Hs578t human breast cancer cells.

Chang, J; Lee, C; Hahm, KB; Yi, Y; Choi, SG; Kim, SJ
Oncogene, 19(1):151-154, 2000
Journal Title
The epithelium-specific transcription factor, ERT/ESX/ESE-1/ELF3, binds to the TGF-beta RII promoter in a sequence specific manner and regulates its expression. In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells. Analyses of the Hs578t parental cell line revealed low RII mRNA expression and resistance to the growth inhibitory effects of TGF-beta. Infection of this cell line with a retroviral construct expressing ERT induced higher levels of endogenous RII mRNA expression and protein expression relative to cells infected with chloramphenicol acetyltransferase (CATneo) as a control. Relative to control cells, the ERTneo-expressing Hs578t cells show approximately a 50% reduction in cell growth in the presence of exogenous TGF-beta1, as well as a fourfold higher induction of activation in transient transfection assays using the 3TP-luciferase reporter construct. When transplanted into athymic mice, ERT-expressing Hs578t cells showed decreased and delayed tumorigenicity compared with control cells. This data strongly suggests that ERT plays an important role as a transcriptional activator of TGF-beta RII expression, and that deregulated ERT expression may play a critical role in rendering Hs578t human breast cancer cells insensitive to TGF-beta's growth inhibitory effects.
MeSH terms
AnimalsBreast Neoplasms/*drug therapy/pathology*DNA-Binding ProteinsFemaleHumansMiceMice, NudeProtein-Serine-Threonine KinasesProto-Oncogene Proteins/*physiologyReceptors, Transforming Growth Factor beta/*geneticsTrans-Activators/*physiologyTranscription Factors/*physiologyTransforming Growth Factor beta/*pharmacology
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
AJOU Authors
함, 기백
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