Transforming growth factor-β pathway activity in glioblastoma

التفاصيل البيبلوغرافية
العنوان: Transforming growth factor-β pathway activity in glioblastoma
المؤلفون: Dorothee Gramatzki, Isabel Tritschler, Michael Weller, Larisa Espinoza, Karl Frei, Judith Johanna Schroeder, Elisabeth J. Rushing
المساهمون: University of Zurich, Weller, M
المصدر: Oncotarget
بيانات النشر: Impact Journals, LLC, 2015.
سنة النشر: 2015
مصطلحات موضوعية: 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
الوصف: 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.
وصف الملف: Sammelmappe1.pdf - application/pdf
DOI: 10.5167/uzh-110458
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9373671026393dae8700d700594a5d5b
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....9373671026393dae8700d700594a5d5b
قاعدة البيانات: OpenAIRE