Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes
Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes
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DOI：
10.1093/carcin/bgn145
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发表时间：
2008-07-01
期刊：
影响因子：
4.7
通讯作者：
Delvenne, Philippe O.
中科院分区：
文献类型：
--
作者：
Caberg, Jean-Hubert D.;Hubert, Pascale M.;Delvenne, Philippe O.
人乳头瘤病毒（HPV）感染，尤其是16型，与子宫颈癌有因果关系。宫颈病变的持续存在或进展表明病毒抗原未能充分呈递给免疫系统。大多数鳞状上皮内病变显示朗格汉斯细胞（LCs）在数量和功能上发生改变，这一观察结果进一步支持了这一假说。此外，在宫颈HPV16相关的（癌前）肿瘤性病变中，朗格汉斯细胞与角质形成细胞（KCs）之间依赖E - 钙黏蛋白的黏附作用存在缺陷。通过RNA干扰（siRNA）沉默HPV16 E7，研究了病毒癌蛋白E7在细胞表面E - 钙黏蛋白水平降低中可能起到的作用。这种处理使HPV16阳性角质形成细胞的细胞表面E - 钙黏蛋白表达增加，并使朗格汉斯细胞与这些鳞状细胞之间的黏附作用显著增强。HPV16 E7沉默后E - 钙黏蛋白的重新表达与视网膜母细胞瘤蛋白和激活蛋白（AP）-2α转录因子的检测水平升高有关。这些数据表明，HPV16 E7诱导的朗格汉斯细胞/角质形成细胞黏附改变可能在宫颈癌发生过程中的免疫应答缺陷中起作用。
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The persistence or progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most squamous intra-epithelial lesions show quantitative and functional alterations of Langerhans cells (LCs). Moreover, E-cadherin-dependent adhesion of LC to keratinocytes (KCs) is defective in cervical HPV16-associated (pre)neoplastic lesions. The possible role of viral oncoprotein E7 in the reduced levels of cell surface E-cadherin was investigated by silencing HPV16 E7 by RNA interference (siRNA). This treatment induced an increased cell surface E-cadherin expression in HPV16-positive KC and a significant adhesion of LC to these squamous cells. The E-cadherin re-expression following HPV16 E7 silencing was associated with increased detection levels of retinoblastoma protein and the activating protein (AP)-2 alpha transcription factor. These data suggest that HPV16 E7-induced alterations of LC/KC adhesion may play a role in the defective immune response during cervical carcinogenesis.