Transforming growth factor-β pathway activity in glioblastoma
| Autor: | Dorothee Gramatzki, Isabel Tritschler, Michael Weller, Larisa Espinoza, Karl Frei, Judith Johanna Schroeder, Elisabeth J. Rushing |
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| Přispěvatelé: | University of Zurich, Weller, M |
| Rok vydání: | 2015 |
| Předmět: |
Gene isoform
TGF-β Adult Male Adolescent medicine.medical_treatment 10208 Institute of Neuropathology PAI-1 610 Medicine & health SMAD Young Adult Transforming Growth Factor beta medicine Biomarkers Tumor Humans Phosphorylation Child Cells Cultured Aged Aged 80 and over Messenger RNA biology business.industry Brain Neoplasms Growth factor glioblastoma Infant Transforming growth factor beta PDGF-B Middle Aged 10040 Clinic for Neurology Oncology Child Preschool biology.protein Cancer research biomarker 2730 Oncology Female Neoplasm Recurrence Local business Plasminogen activator Platelet-derived growth factor receptor Transforming growth factor Research Paper |
| Zdroj: | Oncotarget |
| DOI: | 10.5167/uzh-110458 |
| Popis: | 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 is little contemporary data on the differential expression of TGF-β isoforms at the mRNA and protein level or TGF-β/Smad pathway activity in glioblastomas in vivo. Here we studied 64 newly diagnosed and 16 recurrent glioblastomas for the expression of TGF-β1-3, platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor (PAI)-1 mRNA by RT-PCR and for the levels of TGF-β1-3 protein, phosphorylated Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry. Among the TGF-β isoforms, TGF-β1 mRNA was the most, whereas TGF-β3 mRNA was the least abundant. TGF-β1-3 mRNA expression was strongly correlated, as was the expression of TGF-β1-3 mRNA, and of the TGF-β1-3 target genes, PDGF-B and PAI-1. TGF-β2 and TGF-β3 protein levels correlated well, whereas the comparison of the other TGF-βisoforms did not. Positive correlation was also observed between TGF-β1 and pSmad1/5/8 and between pSmad2 and pSmad1/5/8. Survival analyses indicated that a group of patients with high expression levels of TGF-β2 mRNA or pSmad1/5/8 protein have inferior outcome. We thus provide potential biomarkers for patient stratification in clinical trials of anti-TGF-β therapies in glioblastoma. |
| Databáze: | OpenAIRE |
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