Alonso Marta M, Fueyo Juan, Yung W K Alfred, Gomez-Manzano Candelaria
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cell Cycle. 2006 May;5(9):930-5. doi: 10.4161/cc.5.9.2698. Epub 2006 May 1.
Cancer arises from a stepwise accumulation of genetic changes. Among these changes, deregulation of the Rb/E2F1 pathway and constitutively active telomerase are pivotal milestones for the attainment of immortality and maintaining the neoplastic phenotype. We recently showed the Rb/E2F1 pathway to be a direct modulator of telomerase activity in normal and cancer cells, specifically in malignant gliomas. In addition, we reported that the correlation between the levels of expression of E2F1 and hTERT -the catalytic subunit of telomerase- in a subset of patients with glioblastoma multiforme confers clinical relevance to the role of E2F1 in triggering or maintaining hTERT expression. Here we review the evidence supporting the mechanistic linkage between E2F1 and telomerase activation. We also consider the clinical implications of this association in terms of prognostic significance and opportunities for the development of new and more rational therapeutic strategies.
癌症源于基因变化的逐步积累。在这些变化中，Rb/E2F1通路的失调和持续激活的端粒酶是实现永生化和维持肿瘤表型的关键里程碑。我们最近发现，Rb/E2F1通路是正常细胞和癌细胞中端粒酶活性的直接调节因子，尤其是在恶性胶质瘤中。此外，我们报道，在多形性胶质母细胞瘤患者的一个亚组中，E2F1和端粒酶催化亚基hTERT的表达水平之间的相关性赋予了E2F1在触发或维持hTERT表达中的作用以临床相关性。在这里，我们回顾了支持E2F1与端粒酶激活之间机制联系的证据。我们还从预后意义以及开发新的、更合理治疗策略的机会方面考虑了这种关联的临床意义。
