Holcik M, Yeh C, Korneluk R G, Chow T
Apoptogen Inc., 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada.
Oncogene. 2000 Aug 24;19(36):4174-7. doi: 10.1038/sj.onc.1203765.
Inhibitory regulators of apoptosis play a critical role in the responsiveness of tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins. Here we show that acute low dose ionizing irradiation results in the translational upregulation of XIAP that correlates with an increased resistance to radiation in non-small cell lung carcinoma. This upregulation is mediated by an internal ribosome binding mechanism via an IRES element located within a XIAP 5' UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant to low dose gamma-irradiation. By contrast, the antisense targeting of XIAP resulted in increased cell death following irradiation advocating a distinct role for XIAP in radiation resistant phenotype of human cancers. Oncogene (2000) 19, 4174 - 4177
凋亡抑制调节因子在肿瘤细胞对细胞毒性药物的反应中起关键作用。X连锁凋亡抑制蛋白（XIAP）是凋亡抑制蛋白（IAP）新家族的成员。在此我们表明，急性低剂量电离辐射导致XIAP的翻译上调，这与非小细胞肺癌对辐射的抗性增加相关。这种上调是通过位于XIAP 5'非翻译区的内部核糖体进入位点元件，由内部核糖体结合机制介导的。XIAP的瞬时过表达使人类癌细胞对低剂量γ辐射产生抗性。相比之下，XIAP的反义靶向导致辐射后细胞死亡增加，这表明XIAP在人类癌症的抗辐射表型中具有独特作用。《癌基因》（2000年）第19卷，4174 - 4177页
