Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN):: A natural disease model provides insights into viral carcinogenesis
Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN):: A natural disease model provides insights into viral carcinogenesis
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DOI：
10.1016/j.ejca.2004.11.023
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发表时间：
2005-03-01
影响因子：
8.4
通讯作者：
Khan, S
中科院分区：
文献类型：
--
作者：
Ferris, RL;Martinez, I;Khan, S
关于人乳头瘤病毒（hpv）在头颈部鳞状细胞癌（SCCHN）中的因果关系的不确定性需要更好的体外模型。我们对一种新型的，自然转化HPV-16的SCCHN细胞系（UPCI:SCCO90）进行了分子分析，显示出HPV-16 DNA的高拷贝数，出现在从头到尾，串联重复整合状态。UPCI:SCC090中HPV-16长控制区（LCR）的序列分析显示缺失163 bp，删除了部分增强子序列，包括转录因子YY1和NF1的结合位点。通过定量逆转录聚合酶链反应（RTPCR）确定，HPV-16的E6和E7癌基因在该细胞系中高水平表达。UPCLSCC090含有野生型肿瘤抑制因子TP53基因，p53蛋白检测不到，除非使用顺铂、特异性蛋白酶体抑制剂或E6 RNA干扰，提示该细胞系中p53依赖于E6降解。我们的研究结果与HPV-16在SCCHN发病机制中的致病作用一致。(c) 2005 Elsevier Ltd版权所有。
Uncertainty regarding the causality of human papillomaviruses (HPVs) in squamous cell carcinoma of the head and neck (SCCHN) necessitates better in vitro models. We carried out molecular analyses of a novel, naturally HPV-16-transformed SCCHN cell line (UPCI:SCCO90) and show high copy number of HPV-16 DNA, present in a head to tail, tandemly repeated integrated state. Sequence analysis of the HPV-16 long control region (LCR) in UPCI:SCC090 revealed a deletion of 163 bp, removing a portion of the enhancer sequence, including the binding sites for the transcription factors YY1 and NF1. The E6 and E7 oncogenes of HPV-16 are expressed at high levels in this cell lines, as determined by quantitative reverse transcriptase-polymerase chain reaction (RTPCR). UPCLSCC090 contains wild-type tumour suppressor TP53 gene, and undetectable p53 protein, except after treatment with cisplatin, specific proteasome inhibitors or by E6 RNA interference, suggesting E6-dependent degradation of p53 in this cell line. The results of our studies are consistent with a causative role of HPV-16 in the pathogenesis of SCCHN. (c) 2005 Elsevier Ltd. All rights reserved.