TGF-alpha differentially regulates GFAP, vimentin, and nestin gene expression in U-373 MG glioblastoma cells: correlation with cell shape and motility.
To begin understanding the regulation and biological significance of changes in the expression of intermediate filament proteins in astrocytic tumors, we have recently shown that TGF-alpha alters the protein level of glial fibrillary acidic protein (GFAP), nestin, and vimentin in U-373 MG glioblastoma cells. Here, we have determined the molecular mechanisms regulating these changes. In addition, to evaluate the significance of these changes we have examined whether TGF-alpha affects various cellular properties related to differentiation. Our results show that, in U-373 MG cells treated with TGF-alpha, GFAP gene transcription, mRNA level, and specific protein synthesis decrease by approximately 50%. This suggests that, in U-373 MG cells, TGF-alpha down-regulates the expression of this marker of astrocytic differentiation at the transcriptional level, resulting in decreased GFAP mRNA level and specific protein synthesis. In contrast, TGF-alpha does not change vimentin gene transcription, but increases by about 50% the transcription of the gene for nestin, a marker for undifferentiated astrocytic precursors. This differential regulation of GFAP, nestin, and vimentin gene expression indicates that TGF-alpha induces further dedifferentiation of U-373 MG cells. This notion is also supported by our findings that TGF-alpha increases the motility of U-373 MG cells and induces a less stellate morphology.
Zhou
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Department of Anatomy and Cell Biology, University of Illinois at Chicago, 808 South Wood Street, M/C 512, Chicago, Illinois 60612, USA.
Skalli
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O
D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D005909:Glioblastoma; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D064231:Nestin; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D014746:Vimentin