TGF-α Differentially Regulates GFAP, Vimentin, and Nestin Gene Expression in U-373 MG Glioblastoma Cells: Correlation with Cell Shape and Motility

Abstract

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-α 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-α affects various cellular properties related to differentiation. Our results show that, in U-373 MG cells treated with TGF-α, GFAP gene transcription, mRNA level, and specific protein synthesis decrease by ∼50%. This suggests that, in U-373 MG cells, TGF-α 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-α 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-α induces further dedifferentiation of U-373 MG cells. This notion is also supported by our findings that TGF-α increases the motility of U-373 MG cells and induces a less stellate morphology.