Hassounah Maher, Lach Boleslaw, Allam Ayman, Al-Khalaf Huda, Siddiqui Yunus, Pangue-Cruz Nancy, Al-Omeir Abeer, Al-Ahdal Mohammed N, Aboussekhra Abdelilah
Department of Neurosciences, MBC# 76, Riadh, KSA.
J Neurooncol. 2005 May;72(3):203-8. doi: 10.1007/s11060-004-2397-4.
Survivin, an inhibitor of apoptosis, is over-expressed in foetal tissues and human cancers, but it is almost undetectable in normal tissues. Here we have assessed the level of the survivin protein in some benign tumors of the nervous system: meningioma, schwannoma, low-grade ependymoma, pilocytic astrocytoma and pituitary adenoma. Using immuno-blot analysis we present evidence that these low-grade tumors are positive for survivin expression. In agreement, flow cytometrical analysis showed that both spontaneous and radiation-induced apoptosis levels are very low in these neoplasms. Using host cell reactivation assay we have also shown that these tumor cells are proficient in the repair of gamma-ray-induced DNA damage. However, they are deficient in the removal of ultraviolet (UV) light-induced DNA photolesions, especially the shwannoma- and the pituitary adenoma-derived cells. These results suggest that survivin overexpression may be an early event in the stepwise tumoregenesis and hence could be responsible for the onset as well as the growth advantage during tumoregenic progression of malignant as well as benign neoplasms.
存活素作为一种凋亡抑制因子,在胎儿组织和人类癌症中过度表达,但在正常组织中几乎检测不到。在此,我们评估了存活素蛋白在一些神经系统良性肿瘤中的水平,这些肿瘤包括脑膜瘤、神经鞘瘤、低级别室管膜瘤、毛细胞型星形细胞瘤和垂体腺瘤。通过免疫印迹分析,我们证实这些低级别肿瘤中存活素表达呈阳性。同样,流式细胞仪分析表明,这些肿瘤中自发凋亡和辐射诱导凋亡水平都非常低。利用宿主细胞再激活试验,我们还发现这些肿瘤细胞在修复γ射线诱导的DNA损伤方面表现良好。然而,它们在清除紫外线诱导的DNA光损伤方面存在缺陷,尤其是神经鞘瘤和垂体腺瘤来源的细胞。这些结果表明,存活素的过度表达可能是肿瘤逐步发生过程中的早期事件,因此可能在恶性和良性肿瘤的肿瘤发生进展过程中对肿瘤的起始和生长优势起到作用。