Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription

Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription
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DOI:
10.1007/s001090100211
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发表时间:
2001-06-01
影响因子:
4.7
通讯作者:
Hoppe-Seyler, F
Hoppe-Seyler, F
中科院分区:
医学2区
文献类型:
--
作者:
Beger, M;Butz, K;Hoppe-Seyler, F

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AP-2转录因子家族由三个已知成员组成,即AP-2α、AP-2β和AP-2γ在实验系统中,AP-2因子具有肿瘤抑制物样活性,并且一些肿瘤实体的AP-2表达模式发生了变化。此外,AP-2还参与了人乳头瘤病毒(HPV)的转录调控。我们研究了AP-2α、AP-2β和AP-2γ以及细胞内AP-2靶基因c-erbB-2在一系列宫颈癌细胞系中的表达模式。此外,我们还分析了AP-2因子对HPV16和HPV18 E6/E7癌基因启动子活性的影响。我们发现,除了HPV阴性的C33A细胞外,所有研究的宫颈癌细胞株都表达所有三个AP-2家族成员,尽管表达水平不同。AP-2和c-erb B-2之间无直线相关关系。在报告基因检测中,虽然AP-2α、AP-2β和AP-2γ能激活c-erbB-2启动子,但它们不能激活HPV 16或HPV 18 E6/E7启动子。这些结果表明,尽管这是一种罕见的事件,但在宫颈癌细胞中发生了AP-2表达的缺失。此外,AP-2α、AP-2β和AP-2γ既不足以激活病毒E6/E7启动子,也不是激活病毒E7启动子所必需的。
The AP-2 family of transcription factors consists of three known members, namely AP-2 alpha, AP-2 beta, and AP-2 gamma In experimental systems AP-2 factors, possess tumor suppressor-like activities, and alterations in the AP-2 expression pattern have been described for some tumor entities. In addition, AP-2 has been implicated in the transcriptional control of human papillomaviruses (HPVs). We investigated here the expression pattern of AP-2 alpha, AP-2 beta, and AP-2 gamma, as well as that of the cellular AP-2 target gene c-erbB-2, in a series of cervical cancer cell lines. In addition, we analyzed the influence of AP-2 factors on the activity of the HPV16 and HPV18 E6/E7 oncogene promoter. We found that, with the exception of HPV-negative C33A cells, all investigated cervical cancer cell lines expressed all three AP-2 family members, although at varying levels. No linear correlation between AP-2 and c-erbB-2 levels was observed. Although AP-2 alpha, AP-2 beta, and AP-2 gamma can activate the c-erbB-2 promoter in reporter gene assays, they do not stimulate the HPV 16 or HPV 18 E6/E7 promoter. These results indicate that, although a rare event, loss of AP-2 expression occurs in cervical cancer cells. Moreover, AP-2 alpha., AP-2 beta, and AP-2 gamma are neither sufficient nor required to activate the viral E6/E7 promoter.