Häfner N, Driesch C, Gajda M, Jansen L, Kirchmayr R, Runnebaum I B, Dürst M
Frauenklinik der Friedrich-Schiller-Universität, Jena, Germany.
Oncogene. 2008 Mar 6;27(11):1610-7. doi: 10.1038/sj.onc.1210791. Epub 2007 Sep 10.
Virus integration into the host genome is a characteristic step during cervical carcinogenesis. Experimental data provide evidence that integration could result in increased levels of oncogene (E6/E7) transcripts. This is the first study in which the level of viral transcripts is correlated to the physical state of the viral genome in cervical intraepithelial neoplasia (CIN) and cervical carcinomas (CxCa). Using the APOT-assay integrate-derived transcripts only were detected in 3/28 (11%) CIN and in 28/55 (51%) carcinomas, respectively. The remaining biopsies contained either episome-derived transcripts only or both mRNA species. SybrGreen real time reverse transcriptase-PCR assays were used to quantify viral gene expression for (i) all transcripts initiated from p97, (ii) full-length E6, (iii) E6*I and (iv) E5 transcripts. E6/E7 transcript levels showed a broad distribution but similar median values irrespective of histopathological grading and physical state of the viral genome. Biopsies with integrate-derived transcripts only generally lacked E5-specific mRNA. Our data do not support the hypothesis that HPV integration invariably results in high levels of oncogene transcripts. Instead, constitutive expression of oncogene transcripts rather than the level of expression appears to be decisive for transformation and the maintenance of the malignant phenotype.
病毒整合入宿主基因组是宫颈癌发生过程中的一个特征性步骤。实验数据表明，整合可能导致癌基因（E6/E7）转录本水平升高。这是第一项将病毒转录本水平与宫颈上皮内瘤变（CIN）和宫颈癌（CxCa）中病毒基因组的物理状态相关联的研究。使用APOT分析，分别在3/28（11%）的CIN和28/55（51%）的癌组织中仅检测到整合体衍生的转录本。其余活检组织仅含有游离型衍生的转录本或两种mRNA类型。使用SybrGreen实时逆转录聚合酶链反应分析来定量病毒基因表达，用于（i）所有从p97起始的转录本，（ii）全长E6，（iii）E6*I和（iv）E5转录本。无论组织病理学分级和病毒基因组的物理状态如何，E6/E7转录本水平呈现广泛分布但中位数相似。仅含有整合体衍生转录本的活检组织通常缺乏E5特异性mRNA。我们的数据不支持HPV整合总是导致癌基因转录本高水平的假设。相反，癌基因转录本的组成性表达而非表达水平似乎对转化和恶性表型的维持起决定性作用。
