期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 27, 页码 20315-20323出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M909046199
关键词
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资金
- NCI NIH HHS [CA63783, CA67888, CA76173] Funding Source: Medline
EGR-1, a transcription factor with important functions in the regulation of growth and differentiation, is highly expressed in brain. Previous studies have shown that EGR-1 suppresses the transformed phenotype, However, the expression and role of EGR-1 in human glioblastoma cells are not yet determined. In this study, we found that the basal expression of the EGR-1 protein is undetectable, but is inducible in four human glioblastoma cell lines. To determine EGR-1 functions, we reexpressed EGR-1 in human glioblastoma U251 cells and found that the secretion of transforming growth factor-beta 1 (TGF-beta 1), plasminogen activator inhibitor-1 (PAI-1), and fibronectin (FN) was greatly enhanced. Addition of anti-TGF-beta antibodies completely inhibited the secretion of PAI-1, but had little effect on secretion of FN, indicating that PAI-1 is under the control of EGR-1-induced TGF-beta 1. An examination of the promoter of the FN gene revealed two EGR-1-binding sites between positions -75 and -52 and positions -4 and +14 that specifically bound EGR-1 in gel mobility shift experiments. Utilizing wild-type and mutant FN promoter/luciferase reporter genes, we demonstrated that EGR-1 positively regulated the activity of the FN gene. In addition, cell adhesion and migration were greatly increased in the EGR-1-expressing cells, and adhesion was reversed by addition of RGD-containing peptides, These results suggest that EGR-1 may regulate cell interaction with the extracellular matrix by coordinated induction of TGF-beta 1, FN, and PAI-1 in human glioblastoma cells.
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