<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects"^^ . "Persistent infections with high-risk human papillomaviruses (hr-HPVs) may cause cervical and other types of cancer. The key event for the transformation of hr-HPV-infected cells into malignant tumor cells is the deregulated expression of the hr-HPV oncogenes E6 and E7. Both gene products interfere with cell cycle checkpoints, inhibit DNA damage repair and induce chromosomal instability. Deregulation of hr-HPV oncogene expression as well as transformation of the host cells are driven by the hypermethylation of specific CpG dinucleotides in the viral and host cellular genome. Thereby, the HPV E2-mediated control of E6 and E7 transcription is disrupted and the expression of host cellular tumor suppressive genes and microRNAs is prevented. Therefore, we hypothesized that the application of demethylating agents might re-establish these regulatory mechanisms reducing the hr-HPV oncogene expression and inhibiting cell proliferation.\r\n\r\nTo test this hypothesis, the demethylating agent 5-aza-2’-deoxycytidine (DAC) was applied to a panel of six HPV-transformed cell lines. DAC treatment significantly decreased the expression of the HPV oncogenes. As a consequence, the levels of E6 and E7 target proteins, including p53 and p21, increased repressing cell proliferation and colony formation. In addition, the application of DAC strongly induced the expression of tumor suppressive miR-375, which was shown to target and degrade E6 and E7 transcripts. In conclusion, the presented data demonstrate the effectiveness of DAC in the treatment of HPV-transformed cells and suggest its testing in clinical trials.\r\n\r\nIn addition to the evaluation of treatment strategies, the present thesis aimed to study the effects of HPV oncogene expression on chromosomal stability, gene expression patterns and DNA methylation levels. For this, chromosomally stable HCT116 cells were used as a model system to generate clones allowing the inducible HPV 16 E6 and E7 expression. Immortalization of HCT116 cells, which is characterized by microsatellite instability, can be clearly distinguished from HPV-driven immortalization, which depends on the induction of chromosomal instability. Therefore, HCT116 cells represent an ideal model system to study the HPV 16 oncogene-mediated induction of chromosomal instability.\r\n\r\nInduction of HPV 16 oncogene expression affected the chromosomal stability of HCT116 cells by causing abnormal centrosome and spindle pole numbers, by inducing DNA damage and by increasing the number of aneuploid cells. Furthermore, a panel of genes was found to be differentially expressed after induction of HPV 16 oncogene expression potentially representing candidate genes and indicating pathways that might play a role during the transformation of HPV-infected cells. Taken together, HPV 16 oncogene expression seems to increase the genomic variability in the cell population presumably elevating the risk for the generation of highly proliferative subclones over time."^^ . "2018" . . . . . . . "Lennard"^^ . "Ganß"^^ . "Lennard Ganß"^^ . . . . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (PDF)"^^ . . . "Dissertation Lennard Ganß.pdf"^^ . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (Other)"^^ . . . . . . "small.jpg"^^ . . . "Oncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #24378 \n\nOncogenic potential of HPV E6 and E7 and evaluation of treatment strategies inhibiting their effects\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . . . "600 Technik, Medizin, angewandte Wissenschaften"@de . "600 Technology (Applied sciences)"@en . .