Transforming growth factor-? pathway activity in glioblastoma.

ABSTRACT: Transforming growth factor (TGF)-? is a central molecule maintaining the malignant phenotype of glioblastoma. Anti-TGF-? strategies are currently being explored in early clinical trials. Yet, there is little contemporary data on the differential expression of TGF-? isoforms at the mRNA and protein level or TGF-?/Smad pathway activity in glioblastomas in vivo.Here we studied 64 newly diagnosed and 16 recurrent glioblastomas for the expression of TGF-?1-3, platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor (PAI)-1 mRNA by RT-PCR and for the levels of TGF-?1-3 protein, phosphorylated Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry.Among the TGF-? isoforms, TGF-?1 mRNA was the most, whereas TGF-?3 mRNA was the least abundant. TGF-?1-3 mRNA expression was strongly correlated, as was the expression of TGF-?1-3 mRNA, and of the TGF-?1-3 target genes, PDGF-B and PAI-1. TGF-?2 and TGF-?3 protein levels correlated well, whereas the comparison of the other TGF-?isoforms did not. Positive correlation was also observed between TGF-?1 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-?2 mRNA or pSmad1/5/8 protein have inferior outcome.We thus provide potential biomarkers for patient stratification in clinical trials of anti-TGF-? therapies in glioblastoma.

SUBMITTER: Frei K 

PROVIDER: S-EPMC4467414 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature