Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes.
Papillomaviruses cause certain common human cancers, most notably carcinoma of the cervix. The viral oncoproteins E6 and E7 are essential components in malignant conversion, although, in spite of being necessary, they are not sufficient for the development of the malignant phenotype. High risk HPV oncogenes fulfill dual functions in genome-harboring cells: their derived oncoproteins stimulate cell growth by pleiotropic effects. At the same time they act as progression factors by inducing mutations in host cell DNA and aneuploidy. The mechanism underlying the process towards malignant conversion, usually covering a long latency period between primary infection and cancer emergence, is presently not fully understood. It emerges, however, that cancer development depends on the interruption of at least two signalling cascades (labeled as CIF I and CIF II) that interfere with the function of viral oncoproteins (CIF I) and with the transcription of viral oncogenes (CIF II). Further modifications of host cell genes most likely mediate the escape from immune surveillance mechanisms of the host and the development of metastases.
zur Hausen
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Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.
D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000633:toxicity; D009857:Oncogenes; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; C068651:E6 protein, Human papillomavirus type 16; D008869:Microtubule-Associated Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D050760:Cyclin-Dependent Kinase Inhibitor p27