Ueda T, Akiyama N, Sai H, Oya N, Noda M, Hiraoka M, Kizaka-Kondoh S
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
FEBS Lett. 2001 Feb 23;491(1-2):40-4. doi: 10.1016/s0014-5793(01)02145-7.
Transcriptional promoters responsive to low doses of X-irradiation may be useful in developing a new strategy in gene therapy combined with conventional radiotherapy. The retrovirus-mediated gene trap screening identified c-IAP2 as one of genes possessing such promoters. The analysis of the cis-elements responsive to X-irradiation in c-IAP2 promoter revealed that the NF-kappaB binding sites were necessary and sufficient for the X-ray-responsiveness. We constructed the plasmid p4NFB-BAX, which had four tandem repeats of the NF-kappaB binding sites of c-IAP2 promoter (4NFB) and a suicide gene BAX under the control of 4NFB. The human tumor cells transfected with p4NFB-BAX significantly reduced the number of cells that survived 2 Gy irradiation.
对低剂量X射线辐射有反应的转录启动子可能有助于开发一种与传统放疗相结合的基因治疗新策略。逆转录病毒介导的基因陷阱筛选确定c-IAP2是拥有此类启动子的基因之一。对c-IAP2启动子中对X射线辐射有反应的顺式元件的分析表明，NF-κB结合位点对于X射线反应性是必要且充分的。我们构建了质粒p4NFB-BAX，其具有c-IAP2启动子的NF-κB结合位点（4NFB）的四个串联重复序列以及在4NFB控制下的自杀基因BAX。用p4NFB-BAX转染的人肿瘤细胞显著减少了在2 Gy辐射后存活的细胞数量。
