title: Prognostic impact of the expression/phosphorylation of the BH3-only proteins of the BCL-2 family in glioblastoma multiforme.
abstract: Apoptosis has a crucial role in anti-cancer treatment. The proteins of the BCL-2 family are core members of the apoptotic program. Thus, we postulated that alterations in the expression of BCL-2 protein family, and in particular in that of the Bcl-2 homology domain 3 (BH3)-only proteins (which can neutralized anti-apoptotic proteins or activate pro-apoptotic proteins) could account for differences in the overall survival (OS) of patients. To test this hypothesis, we analyzed the expression of 15 members of the BCL-2 protein family (Bax, Bak, Bok, Bcl-2, Bcl-xl, Bcl-w, Mcl-1, Bad, Bid, Bim, Bik, Bmf, Hrk, Noxa and Puma) in glioblastoma multiforme (GBM) tumors, the most frequent brain tumor in adults. We found that none of the individual expression of these proteins is associated with a significant variation in OS of the patients. However, when all BH3 proteins were pooled to determine a BH3(score), this score was significantly correlated with OS of GBM patients. We also noted that patients with a have high level of phospho-Bad and phospho-Bim displayed a lower OS. Thus, BH3 scoring/profiling could be used as an independent prognostic factor in GBM when globally analyzed.
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer, CRCNA, Nantes, France. pierrefrancois.cartron@univ-nantes.fr
authors.forename: P F
authors.initials: PF
authors.lastname: Cartron
authors.forename: D
authors.initials: D
authors.lastname: Loussouarn
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: S A
authors.initials: SA
authors.lastname: Martin
authors.forename: F M
authors.initials: FM
authors.lastname: Vallette
mesh_terms: D000368:Aged; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010766:Phosphorylation; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D019253:Proto-Oncogene Proteins c-bcl-2