@article{5d2ece8fe2b4499aa50e38c2ba7b6706,
title = "High TGFβ-Smad Activity Confers Poor Prognosis in Glioma Patients and Promotes Cell Proliferation Depending on the Methylation of the PDGF-B Gene",
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.",
keywords = "SIGNALING",
author = "Alejandra Bruna and Darken, {Rachel S.} and Federico Rojo and Alberto Oca{\~n}a and Silvia Pe{\~n}uelas and Alexandra Arias and Raquel Paris and Avelina Tortosa and Jaume Mora and Jose Baselga and Joan Seoane",
note = "Funding Information: We thank Jonathan M. Yingling from Lilly Research Laboratories for helpful discussion and for providing LY2109761 and Serena Di Cosimo for helpful discussion. We are indebted to D. Park, W.E. Fahl, and D. Trono for reagents. We also thank F{\'a}tima N{\'u}{\~n}ez and the Genomic Core Facility of the Vall d'Hebron Hospital Research Institute; Santiago Ram{\'o}n y Cajal, Jos{\'e} Jim{\'e}nez, Arancha Ortega, and the Pathology Department; and Juan Sahuquillo, Carlos Dom{\'i}nguez, M a Antonia Poca, and the Neurosurgery Department of the Vall d'Hebron Hospital. A.B. is an Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer fellow, and R.S.D. is an EMBO fellow. This work has been supported by the Spanish Ministry of Health grant FIS(PI040766), and European Comission Marie Curie International Reintegration grant (MIRG-CT-2005-017121). ",
year = "2007",
month = feb,
day = "13",
doi = "10.1016/j.ccr.2006.11.023",
language = "English",
volume = "11",
pages = "147--160",
journal = "Cancer Cell",
issn = "1535-6108",
number = "2",
}