Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells
Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells
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DOI：
10.1128/jvi.72.12.9470-9478.1998
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发表时间：
1998-12-01
影响因子：
5.4
通讯作者：
zur Hausen, H
中科院分区：
文献类型：
--
作者：
Rothmann, T;Hengstermann, A;zur Hausen, H
腺病毒的55 kDa E1B蛋白与肿瘤抑制蛋白P53结合并失活，在名为Onyx-015(即dl1520)的腺病毒突变体中不表达。据报道，由于E1B基因缺失导致的突变病毒只能在野生型p53缺失的细胞中复制，因此，dl1520目前正被评估为一种潜在的治疗p53缺陷型癌症的工具。相反，我们在这里报告了dl1520在不同的肿瘤细胞系(U87、RKO、A549、H1299和U373)中的复制与p53状态无关，此外，在含有野生型p53的U2OS细胞中，通过反式表达P53负突变体的过表达抑制了P53介导的转录激活，并没有使细胞允许复制DL1520。最后，我们证明，根据感染的多样性，被删除的病毒能够在原代人类细胞中复制并杀死它们。因此，dl1520在不同细胞类型中生长差异的分子基础仍有待确定。
The 55-kDa E1B protein of adenovirus, which binds to and inactivates the tumor suppressor protein p53, is not expressed in the adenoviral mutant termed ONYX-015 (i.e., dl1520). It was reported that the mutant virus due to a deletion in E1B is able to replicate only in cells deficient for wild-type p53, Accordingly, dl1520 is currently being evaluated as a potential tool in the therapy of p53 deficient cancers. In contrast, we report here that dl1520 replicates independently of the p53 status in various tumor cell lines (U87, RKO, A549, H1299, and U373), In addition, the inhibition of p53-mediated transcriptional activation in wild-type p53 containing U2OS cells, by overexpression bf a transdominant negative p53 mutant, did not render the cells permissive for dl1520 replication. Finally, we show that, depending on the multiplicity of infection, the deleted virus is able to replicate in and to kill primary human cells. Thus, the molecular basis for the growth differences of dl1520 within different cell types remains to be determined.