Transforming growth factor-β pathway activity in glioblastoma.
作者： Karl Frei , Dorothee Gramatzki , Isabel Tritschler , Judith Johanna Schroeder , Larisa Espinoza
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摘要: Transforming growth factor (TGF)-β is a central molecule maintaining the malignant phenotype of glioblastoma. Anti-TGF-β strategies are currently being explored in early clinical trials. Yet, there little contemporary data on differential expression TGF-β isoforms at mRNA and protein level or TGF-β/Smad pathway activity glioblastomas vivo.Here we studied 64 newly diagnosed 16 recurrent for TGF-β1-3, platelet-derived (PDGF)-B, plasminogen activator inhibitor (PAI)-1 by RT-PCR levels TGF-β1-3 protein, phosphorylated Smad2 (pSmad2), pSmad1/5/8 PAI-1 immunohistochemistry.Among isoforms, TGF-β1 was most, whereas TGF-β3 least abundant. strongly correlated, as mRNA, target genes, PDGF-B PAI-1. TGF-β2 correlated well, comparison other TGF-βisoforms did not. Positive correlation also observed between pSmad2 pSmad1/5/8. Survival analyses indicated that group patients with high have inferior outcome.We thus provide potential biomarkers patient stratification trials anti-TGF-β therapies
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