Opposite regulation of the HPV 20-URR and HPV 27-URR promoters by ultraviolet irradiation and cytokines.
Epidemiological evidence implicates ultraviolet radiation and genetic changes (e.g., p53 mutations) as important factors in the etiology of nonmelanoma skin cancer. Little is known about a possible role of cutaneous papillomaviruses in these tumors. We previously reported both positive and negative regulation of the promoter activity of a number of HPV types by UV irradiation. To determine the underlying mechanism, we examined the influence of pro-inflammatory cytokines and MAP-kinases induced by UV irradiation by transfecting the HPV 20-URR and the HPV 27-URR into the RKO, HaCaT and H1299 cell lines expressing wild-type or mutated p53 or lacking p53, respectively. IL-1alpha, IL-1beta, IL-6, IL-17, TNF-alpha, as well as interferon-alpha, -beta and -gamma activated the promoter in the HPV 20-URR but inhibited the HPV 27-URR promoter. The effect of IL-1alpha and UV light was abolished by the addition of IL-1 receptor antagonist. UV irradiation induced a prolonged activation of JNK in HaCaT and H1299 but not in RKO cells, and its dephosphorylation was enhanced in the presence of p53 and the HPV-URRs.
Division for Tumorvirus Characterization, Deutsches Krebsforschungszentrum, INF 280, 69120 Heidelberg, Germany.
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Ruhland
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de Villiers
D000730:Androstadienes / Q000494:pharmacology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000821:virology; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003110:Colonic Neoplasms / Q000821:virology; D016207:Cytokines / Q000494:pharmacology*; D004279:DNA, Viral / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008164:Luminescent Proteins / Q000378:metabolism; D008175:Lung Neoplasms; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D027383:Papillomaviridae / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000528:radiation effects; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays; D000077191:Wortmannin
D000730:Androstadienes; D016207:Cytokines; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D015500:Chloramphenicol O-Acetyltransferase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin