Gurzov E N, Bakiri L, Alfaro J M, Wagner E F, Izquierdo M
Department of Molecular Biology, Facultad de Ciencias, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Oncogene. 2008 Jan 24;27(5):641-52. doi: 10.1038/sj.onc.1210690. Epub 2007 Jul 30.
The activating protein-1 transcription factor, in particular the Jun proteins play critical roles in the regulation of cell proliferation and tumor progression. To study the potential clinical relevance of interfering with JunB expression, we generated retroviruses expressing short hairpin RNA. Reduction of JunB levels causes increased proliferation and tumorigenicity in wild-type murine fibroblasts, whereas in c-Jun knockout cells p53-independent cell cycle arrest and apoptosis are induced. Using melanoma-derived B16-F10 cancer cells the combination of JunB knockdown and c-Jun/JNK inactivation leads to cell cycle arrest and apoptosis-inducing factor-dependent apoptosis. Furthermore, the combined treatment extends survival of mice inoculated with the tumor cells. These results indicate that in the absence of c-Jun, JunB can act as a tumor promoter and inactivation of both, c-Jun and JunB, could provide a valuable strategy for antitumor intervention.
活化蛋白-1转录因子，特别是Jun蛋白，在细胞增殖和肿瘤进展的调控中发挥关键作用。为了研究干扰JunB表达的潜在临床相关性，我们构建了表达短发夹RNA的逆转录病毒。JunB水平的降低会导致野生型小鼠成纤维细胞的增殖和致瘤性增加，而在c-Jun基因敲除细胞中会诱导p53非依赖性细胞周期停滞和凋亡。使用黑色素瘤来源的B16-F10癌细胞，JunB敲低与c-Jun/JNK失活相结合会导致细胞周期停滞和凋亡诱导因子依赖性凋亡。此外，联合治疗可延长接种肿瘤细胞的小鼠的生存期。这些结果表明，在缺乏c-Jun的情况下，JunB可作为肿瘤促进因子，而c-Jun和JunB两者的失活可为抗肿瘤干预提供有价值的策略。
