Conditional expression of exogenous Bcl-Xs triggers apoptosis in human melanoma cells in vitro and delays growth of melanoma xenografts
Conditional expression of exogenous Bcl-Xs triggers apoptosis in human melanoma cells in vitro and delays growth of melanoma xenografts
复制标题
DOI：
10.1016/s0014-5793(03)01017-2
复制
发表时间：
2003-10-23
期刊：
影响因子：
3.5
通讯作者：
Geilen, CC
中科院分区：
文献类型：
--
作者：
Hossini, AM;Eberle, R;Geilen, CC
Bcl-2相关蛋白Bcl-X-L和Bcl-X-S代表选择性剪接产物，并在细胞凋亡的控制中发挥相反的活性，但它们在黑色素瘤中的意义尚不清楚。应用四环素诱导表达系统Tet-On，我们发现Bcl-X-S本身的过表达足以在体外稳定转染的人黑色素瘤细胞系中诱导凋亡。与促凋亡剂，如依托泊苷，帕米膦酸盐，神经酰胺的组合，导致附加的促凋亡作用，而Bcl-X-L保护通过CD 95/Fas刺激引起的细胞凋亡。在裸鼠中，来自稳定转染细胞的黑素瘤异种移植物的生长在由多西环素诱导Bcl-X-S后显著减少。我们的研究结果表明，Bcl-X蛋白是恶性黑色素瘤细胞凋亡的控制非常重要。(C)2003年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The Bcl-2-related proteins Bcl-X-L and Bcl-X-S represent alternative splice products and exert opposite activities in the control of apoptosis, but their significance for melanoma is not yet clear. Applying the tetracycline-inducible expression system Tet-On, we found overexpression of Bcl-X-S by itself sufficient to induce apoptosis in vitro in stably transfected human melanoma cell lines. Combination with proapoptotic agents such as etoposide, pamidronate, and ceramide resulted in additive proapoptotic effects, whereas Bcl-X-L protected from apoptosis caused via CD95/Fas stimulation. In nude mice growth of melanoma xenotransplants derived from stably transfected cells was significantly reduced after induction of Bcl-X-S by doxycycline. Our results indicate that Bcl-X proteins are of major importance for control of apoptosis in malignant melanoma. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.