High TGFβ-Smad Activity Confers Poor Prognosis in Glioma Patients and Promotes Cell Proliferation Depending on the Methylation of the PDGF-B Gene

Alejandra Bruna, Rachel S. Darken, Federico Rojo, Alberto Ocaña, Silvia Peñuelas, Alexandra Arias, Raquel Paris, Avelina Tortosa, Jaume Mora, Jose Baselga, Joan Seoane

Research output: Contribution to journalArticlepeer-review

377 Scopus citations

Abstract

TGFβ acts as a tumor suppressor in normal epithelial cells and early-stage tumors and becomes an oncogenic factor in advanced tumors. The molecular mechanisms involved in the malignant function of TGFβ are not fully elucidated. We demonstrate that high TGFβ-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma. We discern the mechanisms and molecular determinants of the TGFβ oncogenic response with a transcriptomic approach and by analyzing primary cultured patient-derived gliomas and human glioma biopsies. The TGFβ-Smad pathway promotes proliferation through the induction of PDGF-B in gliomas with an unmethylated PDGF-B gene. The epigenetic regulation of the PDGF-B gene dictates whether TGFβ acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma.

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalCancer Cell
Volume11
Issue number2
DOIs
StatePublished - Feb 13 2007

Keywords

  • SIGNALING

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