GLIOMA · Molecular mechanisms of glioma genesis
6РП — Действия „Мария Кюри“
- Период
- 2005-09-01 → 2007-08-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Молекулярните механизми при глиомите разглеждат как протеинът TGFbeta стимулира размножаването на туморните клетки чрез активиране на гена PDGF-B. Разбирането на този процес помага да се определи прогнозата за състоянието на пациентите.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Glioma is the most common tumour of the brain and its most malignant form, glioblastoma multiforme, is virtually not curable. Very little is known about gliomagenesis and progression at the molecular level and not much progress have been achieved in the discovery of new therapies during the last years. Among others, two signalling pathways are very relevant in glioma, the TGFb pathway and the PDGF pathway. TGFb has two differentiated faces in glioma progression. In low-grade glioma, TGFb is an anti-tumorigen ic factor that mediates the inhibition of proliferation. In high-grade glioma, glioblastoma multiforme, TGFb becomes an oncogenic factor that induces proliferation, invasion, angiogenesis and immuno-supression.Another pathway that is important in the genes is of glioma is the PDGF pathway. PDGF and the PDGF receptor are highly expressed in human glioma and PDGF over-expression promotes the formation of glioma in a mouse model. Our preliminary data indicate that at the crossroad of the PDGF and TGFb pathways there is a transcription factor called FoxG1. FoxG1 is the cellular homologue of an avian sarcoma viral oncogene called Qin. FoxG1 is expressed in neuroprogenitors and glioma but not in differentiated cells. FoxG1 inhibits differentiation and promotes proliferation.We hypothesize that FoxG1 promotes the switch of the TGFb action towards its malignant effects and in part mediates PDGF oncogenesis. In order to test this hypothesis we will undertake three approaches: we will study TGFb,PDGF and FoxG1 molecular interactions in a cell culture model using human glioblastoma cell lines. We will assess their role in glioma progression in a mouse glioma model. And, we will support our findings analysing human tumours from the Vall dHebron Hospital tumour bank. This project aims to clarify the molecular mechanisms of gliomagenesis and to help in the finding of new biomarkers and targets for future and more effective therapies.
Оригинален текст от CORDIS (на английски).
Участници
- VALL DHEBRON UNIVERSITY HOSPITAL RESEARCH INSTITUTE · BARCELONAКоординаторНиво градИспания
Връзки
Данни: CORDIS, © Европейски съюз