Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer, CRCNA, Nantes, France.
Cell Death Dis. 2012 Nov 15;3(11):e421. doi: 10.1038/cddis.2012.150.
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.
细胞凋亡在抗癌治疗中起着至关重要的作用。BCL-2 家族蛋白是细胞凋亡程序的核心成员。因此，我们推测 BCL-2 蛋白家族表达的改变，特别是 Bcl-2 同源结构域 3（BH3）仅蛋白（可中和抗凋亡蛋白或激活促凋亡蛋白）的改变可能导致患者总生存期（OS）的差异。为了验证这一假说，我们分析了 15 种 BCL-2 蛋白家族成员（Bax、Bak、Bok、Bcl-2、Bcl-xl、Bcl-w、Mcl-1、Bad、Bid、Bim、Bik、Bmf、Hrk、Noxa 和 Puma）在多形性胶质母细胞瘤（GBM）肿瘤中的表达，GBM 是成人最常见的脑肿瘤。我们发现这些蛋白的单独表达均与患者 OS 无显著变化相关。然而，当所有 BH3 蛋白被汇集以确定 BH3（评分）时，该评分与 GBM 患者的 OS 显著相关。我们还注意到，磷酸化 Bad 和磷酸化 Bim 水平高的患者 OS 较低。因此，当总体分析时，BH3 评分/分析可作为 GBM 的独立预后因素。
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