title: Role of Btg2 in the progression of a PDGF-induced oligodendroglioma model.
abstract: Tumor progression is a key aspect in oncology. Not even the overexpression of a powerful oncogenic stimulus such as platelet derived growth factor-B (PDGF-B) is sufficient per se to confer full malignancy to cells. In previous studies we showed that neural progenitors overexpressing PDGF-B need to undergo progression to acquire the capability to give rise to secondary tumor following transplant. By comparing the expression profile of PDGF-expressing cells before and after progression, we found that progressed tumors consistently downregulate the expression of the antiproliferative gene Btg2. We therefore tested whether the downregulation of Btg2 is sufficient and necessary for glioma progression with loss and gain of function experiments. Our results show that downregulation of Btg2 is not sufficient but is necessary for tumor progression since the re-introduction of Btg2 in fully progressed tumors dramatically impairs their gliomagenic potential. These results suggest an important role of Btg2 in glioma progression. Accordingly with this view, the analysis of public datasets of human gliomas showed that reduced level of Btg2 expression correlates with a significantly worse prognosis.
authors.affiliation: San Martino-IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. paolo.malatesta@unige.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Appolloni
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Curreli
authors.forename: Sara
authors.initials: S
authors.lastname: Caviglia
authors.forename: Manuela
authors.initials: M
authors.lastname: Barilari
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gambini
authors.forename: Aldo
authors.initials: A
authors.lastname: Pagano
authors.forename: Paolo
authors.initials: P
authors.lastname: Malatesta
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011485:Protein Binding; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D017874:Immediate-Early Proteins; D020574:Proto-Oncogene Proteins c-sis; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human