Gene expression profiles reveal an upregulation of E2F and downregulation of interferon targets by HPV18 but no changes between keratinocytes with integrated or episomal viral genomes
Gene expression profiles reveal an upregulation of E2F and downregulation of interferon targets by HPV18 but no changes between keratinocytes with integrated or episomal viral genomes
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DOI：
10.1016/j.virol.2006.05.030
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发表时间：
2006-09-15
期刊：
影响因子：
3.7
通讯作者：
Stubenrauch, Frank
中科院分区：
文献类型：
--
作者：
Karstensen, Bernd;Poppelreuther, Sven;Stubenrauch, Frank
持续感染 18 型人乳头瘤病毒可导致宫颈癌的发生。 HPV18 基因组在低度和癌前病变中持续存在于染色体外，但总是整合在宫颈癌中，这可能有助于 HPV18 诱导的病变的进展。为了确定整合是否会引起宿主细胞的额外变化，使用高密度寡核苷酸阵列分析了几种具有野生型和复制缺陷型E1突变型HPV18 (E1C-TTL)基因组的角质形成细胞系。与正常角质形成细胞相比，野生型和整合型 E1C-TTL HPV18 基因组解除了 280 个带注释基因的表达调控。然而，野生型与E1C-TTL细胞系的比较没有发现任何显着差异，表明E1的丢失和病毒整合都不会在低传代HPV18阳性角质形成细胞中引起额外的基因表达变化。一半失调基因被描述为 p16/Rb/E2F、p53、干扰素或 NF kappa B 途径的靶标，与病毒 E6 和 E7 癌蛋白的功能一致，但另一半目前不能归因于某些途径。 (c) 2006 Elsevier Inc. 保留所有权利。
Persistent infections with human papillomaviruses type 18 can result in the development of cervical cancer. HPV18 genomes persist extrachromosomally in low-grade and precancerous lesions but are always integrated in cervical cancers, and this might contribute to the progression of HPV18-induced lesions. To address whether integration induces additional changes in host cells, several keratinocyte lines with wild type and replication-deficient El mutant HPV18 (E1C-TTL) genomes were analyzed with high density oligonucleotide arrays. In comparison to normal keratinocytes, wild type and integrated E1C-TTL HPV18 genomes deregulate the expression of 280 annotated genes. However, the comparison of wild type with E1C-TTL cell lines did not reveal any significant differences, indicating that neither the loss of E1 nor viral integration induces additional gene expression changes in low passage HPV18-positive keratinocytes. Half of the deregulated genes have been described as targets of the p16/Rb/E2F, p53, interferon or NF kappa B pathways consistent with the functions ascribed to the viral E6 and E7 oncoproteins, but the other half can currently not be ascribed to certain pathways. (c) 2006 Elsevier Inc. All rights reserved.