Final Activity Report Summary - GLIOMA (Molecular mechanisms of glioma genesis) We have demonstrated that high TGFbeta-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma. We have discerned the mechanisms and molecular determinants of the TGFbeta oncogenic response using a transcriptomic approach and analyzing primary cultured patient-derived gliomas and human glioma biopsies. We have found that the TGFbeta-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 TGFbeta acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma. This work has generated a publication where the contribution of the Marie Curie Reintegration Grant has been acknowledged: A. Bruna, R.S. Darken, F. Rojo, A. Ocaña, S. Peñuelas, A. Arias, R. Paris, A. Tortosa, J. Mora, J. Baselga, J. Seoane, High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene Cancer Cell (2007) 11, 147-160.
