| Title | High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J, Seoane J |
| Journal | Cancer Cell |
| Volume | 11 |
| Issue | 2 |
| Pagination | 147-60 |
| Date Published | 2007 Feb |
| ISSN | 1535-6108 |
| Keywords | Adolescent, Adult, Aged, Astrocytoma, Brain Neoplasms, Cell Proliferation, Child, Child, Preschool, DNA Methylation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma, Glioma, Humans, Infant, Middle Aged, Oligonucleotide Array Sequence Analysis, Phosphorylation, Prognosis, Proto-Oncogene Proteins c-sis, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad2 Protein, Smad7 Protein, Survival Rate, Transforming Growth Factor beta, Tumor Cells, Cultured |
| Abstract | TGFbeta 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 TGFbeta are not fully elucidated. We demonstrate that high TGFbeta-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 TGFbeta oncogenic response with a transcriptomic approach and by analyzing primary cultured patient-derived gliomas and human glioma biopsies. 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. |
| DOI | 10.1016/j.ccr.2006.11.023 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 17292826 |
Submitted by kej2006 on June 6, 2018 - 4:10pm