Dominant role of HPV16 E7 in anal carcinogenesis.

Dominant role of HPV16 E7 in anal carcinogenesis.
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DOI:
10.1016/j.virol.2011.09.018
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发表时间:
2011-12-20
期刊:
影响因子:
3.7
通讯作者:
Lambert PF
Lambert PF
中科院分区:
医学3区
文献类型:
--
作者:
Thomas MK;Pitot HC;Liem A;Lambert PF

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百分之九十的肛门癌与人乳头瘤病毒 (HPV) 有关。使用我们之前建立的肛门癌 HPV 转基因小鼠模型,我们测试了单个癌基因 E6 和 E7 的作用。用二甲基苯并[a]蒽(DMBA)对K14E6和K14E7转基因小鼠进行肛管处理,并与匹配的非转基因和双转基因K14E6/E7小鼠进行比较。 K14E7 和 K14E6/E7 转基因小鼠发生肛门肿瘤(乳头状瘤、异型性和癌的总和)的比率(分别为 88% 和 100%)显着高于 K14E6 或 NTG 小鼠(分别为 18% 和 19%)。同样,K14E7 和 K14E6/E7 转基因小鼠患上癌症的比率(分别为 85% 和 85%)显着高于 K14E6 或 NTG 小鼠(分别为 18% 和 10%)。这些发现表明,E7 是 HPV 引起的肛门癌中更有效的癌基因。
Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared to matched nontransgenic and doubly transgenic K14E6/E7 mice. K14E7 and K14E6/E7 transgenic mice developed anal tumors (papillomas, atypias and carcinomas combined) at significantly higher rates (88% and 100%, respectively) than either K14E6 or NTG mice (18% and 19%, respectively). Likewise, K14E7 and K14E6/E7 transgenic mice developed frank cancer (carcinomas) at significantly higher rates (85% and 85%, respectively) than either K14E6 or NTG mice (18% and 10%, respectively). These findings indicate that E7 is the more potent oncogene in anal cancer caused by HPVs.
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