德國癌癥研究中心3日發(fā)表公報(bào)說，該中心研究人員發(fā)現(xiàn)了宮頸癌病毒破壞人體免疫力的機(jī)理——這種病毒能抑制人體免疫系統(tǒng)中一種信號(hào)分子的基因表達(dá),。這一發(fā)現(xiàn)將有助于研究人員尋找醫(yī)治宮頸癌的新方法,。
人乳頭瘤病毒16型是引發(fā)宮頸癌的最常見病毒。德國癌癥研究中心的科研人員通過觀察培養(yǎng)皿中被這種病毒感染的細(xì)胞發(fā)現(xiàn),，這種病毒的E6基因在宿主細(xì)胞中抑制了其免疫系統(tǒng)信號(hào)物質(zhì)IFNk干擾素的基因表達(dá),。研究人員隨后在宮頸癌組織樣本上做實(shí)驗(yàn)也驗(yàn)證了這一發(fā)現(xiàn)。
干擾素是細(xì)胞在受到病毒感染后分泌的具有抗病毒功能的蛋白質(zhì),。細(xì)胞感染病毒后分泌的干擾素能對周圍未感染細(xì)胞上的相關(guān)受體產(chǎn)生作用,，促使這些細(xì)胞合成抗病毒蛋白質(zhì)防止進(jìn)一步感染。
研究人員指出,，IFNk干擾素能抵抗人乳頭狀瘤病毒,，是因?yàn)樗饕谶@種病毒寄居的上皮細(xì)胞中產(chǎn)生。如果這些細(xì)胞中的IFNk干擾素失靈,，則參與免疫的其他蛋白質(zhì)也會(huì)功能失調(diào),。
研究人員計(jì)劃下一步研究為人體輸入IFNk干擾素，看是否可以抑制宮頸癌細(xì)胞的生長,。
這一成果已發(fā)表在美國《癌癥研究》雜志上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Research 69, 8718, November 15, 2009.doi: 10.1158/0008-5472.CAN-09-0550
Epigenetic Silencing of Interferon-κ in Human Papillomavirus Type 16–Positive Cells
Bladimiro Rincon-Orozco1, Gordana Halec2, Simone Rosenberger1, Dorothea Muschik1, Ingo Nindl1, Anastasia Bachmann3, Tina Maria Ritter1, Bolormaa Dondog4, Regina Ly1, Franz X. Bosch2, Rainer Zawatzky1 and Frank R?sl1
1 Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Universit?t Heidelberg; 2 Molekularbiologisches Labor, Universit?ts-HNO-Klinik Heidelberg; 3 Molecular Alcohol Research in Gastroenterology, Universit?t Heidelberg; and 4 Angewandte Tumorvirologie, Abteilung Genomver?nderungen und Karzinogenese, Deutsches Krebsforschungszentrum, Heidelberg, Germany
We have investigated interferon-κ (IFN-κ) regulation in the context of human papillomavirus (HPV)–induced carcinogenesis using primary human foreskin keratinocytes (HFK), immortalized HFKs encoding individual oncoproteins of HPV16 (E6, E7, and E6/E7), and cervical carcinoma cells. Here, IFN- κ was suppressed in the presence of E6, whereas its expression was not affected in HFKs or E7-immortalized HFKs. Transcription could be reactivated after DNA demethylation but was decreased again upon drug removal. Partial reactivation could also be accomplished when E6 was knocked down, suggesting a contribution of E6 in IFN-κ de novo methylation. We identified a single CpG island near the transcriptional start site as being involved in selective IFN-κ expression. To prove the functional relevance of IFN-κ in building up an antiviral response, IFN-κ was ectopically expressed in cervical carcinoma cells where protection against vesicular stomatitis virus–mediated cytolysis could be achieved. Reconstitution of IFN-κ was accompanied by an increase of p53, MxA, and IFN-κ regulatory factors, which was reversed by knocking down either IFN-κ or p53 by small interfering RNA. This suggests the existence of a positive feedback loop between IFN-κ, p53, and components of IFN signaling pathway to maintain an antiviral state. Our in vitro findings were further corroborated in biopsy samples of cervical cancer patients, in which IFN-κ was also downregulated when compared with normal donor tissue. This is the first report showing an epigenetic silencing of type I IFN after HPV16 oncogene expression and revealing a novel strategy on how high-risk HPVs can abolish the innate immune response in their genuine host cells.
