Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein.
Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein.
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DOI：
10.1186/1750-9378-6-18
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发表时间：
2011-10-27
影响因子：
3.7
通讯作者：
Campisi G
中科院分区：
文献类型：
--
作者：
Rodolico V;Arancio W;Amato MC;Aragona F;Cappello F;Di Fede O;Pannone G;Campisi G
越来越多的证据表明，高危型人乳头状瘤病毒（HPV）在口腔鳞状细胞癌（OSCC）的发病机制中发挥着重要作用。来自HR HPV的E6和E7癌基因负责参与细胞周期和凋亡途径的p53和pRB蛋白的失调。在细胞系实验中，HPV E7蛋白似乎能够增强缺氧诱导因子-1 α（HIF-1α）的活性，通常参与对缺氧的反应并能够增强血管生成。我们研究了62例口腔鳞癌的肿瘤标本，观察到HPV 16 DNA阳性的口腔鳞癌TNM分期II和pT 2级的肿瘤患病率高于未感染的。在整个分析区域检测到HIF-1α阳性，与坏死区域无关，并且在紧邻血管的细胞中也观察到。HPV 16 DNA阳性的肿瘤中pT 1-T2期和I-II期的HIF-1α标记指数均较未感染的肿瘤明显增高。HIF-1α与HPV 16 E7标记指数呈显著正相关，提示HPV 16 E7与HIF-1α表达呈正相关。在我们的标本中，HIF-1α免疫反应性提示在感染的HPV 16 DNA阳性肿瘤中，特别是在pT 1-T2和I-II期肿瘤中，存在一种不依赖于O2的调节机制，这表明HIF-1 α在HPV诱导的OSCC的发展中非常早期。HIF-1α和HPV 16 E7标记指数在HPV 16 DNA阳性的口腔鳞癌中也存在相关性。
There is increasing evidence for the role of High Risk (HR) Human PapillomaVirus (HPV) in the pathogenesis of Oral Squamous Cell Carcinoma (OSCC). The E6 and E7 oncogenes from HR HPVs are responsible for the deregulation of p53 and pRB proteins involved in cell cycle and apoptotic pathways. In cell lines experiments, the HPV E7 protein seems to be able to enhance Hypoxia Inducible Factor-1 alpha (HIF-1α) activity, normally involved in the response to hypoxia and able to enhance angiogenesis. We studied tumor specimens from 62 OSCC; a higher prevalence of tumors in TNM stage II and also in pT2 class between OSCC infected positive HPV16 DNA than non-infected ones was observed. HIF-1α positivity was detected throughout the analysed fields, not associated with areas of necrosis and also observed in cells immediately adjacent to blood vessels. A significant increase in mean values of the HIF-1α labeling indexes was observed for pT1-T2, as well for stage I-II, in the infected positive HPV16 DNA tumors than non-infected ones. HIF-1α and HPV16 E7 labeling indexes showed a significantly positive correlation which suggested a positive association between HPV16 E7 and HIF-1α expression. In our specimens HIF-1α immunoreactivity hints for an O2-independent regulatory mechanism in infected positive HPV16 DNA tumors, especially for pT1-T2 and stage I-II tumors, suggesting a very early involvement in the development of HPV-induced OSCC. HIF-1α and HPV16 E7 labeling indexes suggest also a positive association between the two proteins in infected positive HPV16 DNA OSCC.
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影响因子：
6.4
作者：
Azzimonti, B;Pagano, M;Gariglio, M
通讯作者：
Gariglio, M
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Giovannelli, L;Campisi, G;Ammatuna, P
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Ammatuna, P
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