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宫颈癌组织中HPV16,18E6蛋白表达的观察 总被引:12,自引:0,他引:12
目的观察HPV16、18早期蛋白E6在人宫颈鳞状细胞癌中的表达并评价E6单抗的应用价值。方法采用SP免疫组化染色法,检测40例宫颈鳞状细胞癌,30例慢性宫颈炎及30例正常宫颈组织中HPV16、18E6蛋白的表达。结果癌组中E6的阳性率为67.5%(27/40),慢性宫颈炎中为3.3%(1/30),正常宫颈组织中均为阴性,良、恶组HPV16、18E6的阳性率差异有显著意义(P<0.01)。结论HPV16、18感染与本地区宫颈癌病因学密切相关,E6单抗可作为预测HPV16、18感染及宫颈癌早期诊断的标记之一。 相似文献
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Over the last two decades, since the initial discovery of human papillomavirus (HPV) type 16 and 18 DNAs in cervical cancers by Dr. Harald zur Hausen (winner of the Nobel Prize in Physiology or Medicine, 2008), the HPVs have been well characterised as causative agents for cervical cancer. Viral DNA from a specific group of HPVs can be detected in at least 90% of all cervical cancers and two viral genes, E6 and E7, are invariably expressed in HPV‐positive cervical cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, one function of E6 is to activate telomerase, and E6 and E7 cooperate to effectively immortalise human primary epithelial cells. Though expression of E6 and E7 is itself not sufficient for cancer development, it seems to be either directly or indirectly involved in every stage of multi‐step carcinogenesis. Epidemiological and biological studies suggest the potential efficacy of prophylactic vaccines to prevent genital HPV infection as an anti‐cancer strategy. However, given the widespread nature of HPV infection and unresolved issues about the duration and type specificity of the currently available HPV vaccines, it is crucial that molecular details of the natural history of HPV infection as well as the biological activities of the viral oncoproteins be elucidated in order to provide the basis for development of new therapeutic strategies against HPV‐associated malignancies. This review highlights novel functions of E6 and E7 as well as the molecular mechanisms of HPV‐induced carcinogenesis. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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乳头瘤病毒16型E6,P53,RB,PCNA在宫颈癌中的表达… 总被引:1,自引:0,他引:1
应用核酸原位杂交和免疫组织化学技术,检测人子宫颈癌中人乳头瘤病毒(HPV)16型E6RF与抑癌基因产物P53,RB和增殖细胞核抗原(PCNA)。在44例宫颈癌石蜡切片中,原位杂交检测出HPV16E6ORF阳性27例(61.36%),其中免疫组化检测出P53、RB、PCNA一分别为8例(29.63#),14例(52.85%)、20例(74.07%),而在17例HPV16E6阴性 本中P53、RB、P 相似文献
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High-throughput cervical cancer screening using intracellular human papillomavirus E6 and E7 mRNA quantification by flow cytometry 总被引:2,自引:0,他引:2
The Papanicolaou (Pap) test, based solely on the morphologic examination of exfoliated cells from the cervix, has reduced deaths due to cervical cancer by 74% in the United States during the past 40 years. During that time, the molecular mechanisms of cervical cancer have largely been elucidated. Taken together, these observations have identified a need for a high-throughput cervical cancer screening assay. We report the development of a high-throughput assay consisting of simultaneous immunophenotyping and ultrasensitive in situ hybridization for human papillomavirus (HPV) E6 and E7 messenger RNA (mRNA). This assay can be performed in less than 3 hours directly from liquid-based cervical cytology specimens. Overall, HPV fluorescence in situ hybridization (FISH) for E6 and E7 mRNA demonstrated 83.3% sensitivity and 91.3% specificity for high-grade squamous intraepithelial lesions compared with the Pap test in 231 liquid-based cytology samples from 2 cohorts. In a subset of these samples, HPV FISH demonstrated higher sensitivity and specificity than Hybrid Capture (Digene, Gaithersburg, MD) for high-risk genotypes. 相似文献
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E7-specific cytotoxic T cell tolerance in HPV-transgenic mice 总被引:2,自引:0,他引:2
A. Borchers J. Braspenning J. Meijer W. Osen L. Gissmann I. Jochmus 《Archives of virology》1999,144(8):1539-1556
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Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses 总被引:1,自引:0,他引:1
Kuner R Vogt M Sultmann H Buness A Dymalla S Bulkescher J Fellmann M Butz K Poustka A Hoppe-Seyler F 《Journal of molecular medicine (Berlin, Germany)》2007,85(11):1253-1262
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Peralta-Zaragoza O Bermúdez-Morales V Gutiérrez-Xicotencatl L Alcocer-González J Recillas-Targa F Madrid-Marina V 《Viral immunology》2006,19(3):468-480
Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer. 相似文献
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Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells,promoting radioresistance and cancer aggressiveness
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Thomas Ho‐Yin Leung Hermit Wai‐Man Tang Michelle Kwan‐Yee Siu David Wai Chan Karen Kar‐Loen Chan Annie Nga‐Yin Cheung Hextan Yuen‐Sheung Ngan 《The Journal of pathology》2018,244(2):151-163
Accumulating evidence indicates that the human papillomavirus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Subpopulations of cells that reside within tumours are responsible for tumour resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV‐E6 protein have not been identified. Here, we isolated sphere‐forming cells, which showed self‐renewal ability, from primary cervical tumours. Gene expression profiling revealed that cluster of differentiation (CD) 55 was upregulated in primary cervical cancer sphere cells. Flow‐cytometric analysis detected abundant CD55(+) populations among a panel of HPV‐positive cervical cancer cell lines, whereas few CD55(+) cells were found in HPV‐negative cervical cancer and normal cervical epithelial cell lines. The CD55(+) subpopulation isolated from the C33A cell line showed significant sphere‐forming ability and enhanced tumourigenicity, cell migration, and radioresistance. In contrast, the suppression of CD55 in HPV‐positive CaSki cells inhibited tumourigenicity both in vitro and in vivo, and sensitized cells to radiation treatment. In addition, ectopic expression of the HPV‐E6 protein in HPV‐negative cervical cancer cells dramatically enriched the CD55(+) subpopulation. CRISPR/Cas9 knockout of CD55 in an HPV‐E6‐overexpressing stable clone abolished the tumourigenic effects of the HPV‐E6 protein. Taken together, our data suggest that HPV‐E6 protein expression enriches the CD55(+) population, which contributes to tumourigenicity and radioresistance in cervical cancer cells. Targeting CD55 via CRISPR/Cas9 may represent a novel avenue for developing new strategies and effective therapies for the treatment of cervical cancer. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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We are developing recombinant attenuated vesicular stomatitis virus (VSV) as a vaccine vector to generate humoral and cell-mediated immune responses. Here, we explore the use of VSV vaccines for cancer immunotherapy. Immunotherapy targeting high-risk human papillomavirus (HPV) lesions has the potential to benefit HPV-infected individuals and cervical cancer patients by generating cytotoxic T cells that kill tumor cells that express viral antigens. A single dose of VSV expressing the HPV type 16 (HPV16) E7 oncogene was used for therapeutic vaccination of mice bearing TC-1 syngeneic tumors, which express HPV16 E7. HPV16 E7-specific T cells were generated and displayed cytotoxic activity against the tumor cells. By 14 days postvaccination, average tumor volumes were 10-fold less in the vaccinated group than in mice that received the empty-vector VSV, and regression of preexisting tumors occurred in some cases. This antitumor effect was CD8 T-cell dependent. Our results demonstrate antitumor responses to HPV16 E7 and suggest that recombinant-VSV-based vaccination should be explored as a therapeutic strategy for cervical carcinoma and other HPV-associated cancers. 相似文献
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Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs. 总被引:12,自引:0,他引:12
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J. M. Arbeit K. Münger P. M. Howley D. Hanahan 《The American journal of pathology》1993,142(4):1187-1197
The effect of the human papillomavirus (HPV) oncogenes E6 and E7 was examined in transgenic mice with a construct containing the human beta-actin promoter regulating HPV16 E6 and E7 open reading frames. In the sole line of mice that transmitted the transgene, neuroepithelial tumors appeared at 2.5 months of life, and by 10 months, 87 of 122 (71%) of the animals were dead from brain tumors. The most frequent type of tumor (74%) was an anaplastic neuroepithelial tumor associated with the ependyma of the third and fourth ventricles, which locally invaded adjacent brain tissue and spread for considerable distances along the ventricular surface. The other two types of tumor were well-differentiated choroid plexus carcinomas (26%) and rare pituitary carcinomas (8.7%). HPV16 E6 RNA and E7 oncoprotein expression were demonstrated in tumor tissue and primary cell lines derived from the tumors. Examination of two tumor suppressor gene products, the retinoblastoma protein and p53, known to bind to HPV16 E7 and E6 oncoproteins, respectively, showed both were expressed in the primary tumor cell lines. These data support a causative role for the HPV oncoproteins in epithelial carcinogenesis. 相似文献
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High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins 总被引:4,自引:0,他引:4
We have previously shown that functional components of the NF-kappaB signaling pathway are up-regulated and sequestered in the cytoplasm of human papillomavirus 16 (HPV16)-transformed cell lines leading to a reduced activity of NF-kappaB. In this study, we examined the expression of the NF-kappaB precursors p100 and p105 in keratinocytes transformed or not by HPV16. Western immunoblotting experiments demonstrated high levels of p100 and p105 proteins not only in HPV16+ cervical carcinoma-derived keratinocytes but also in keratinocytes stably transfected by HPV16 E6 or E7 oncogenes. Moreover, p100 and p105 proteins were predominantly cytoplasmic and nuclear in keratinocytes expressing E7 and E6, respectively. A predominantly cytoplasmic localization of E7 protein was also detected in all keratinocytes expressing E7. Our results suggest that HPV16 E6 and E7 proteins modulate the expression and the subcellular localization of p100 and p105 NF-kappaB precursors. 相似文献
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The human papillomavirus (HPV) E7 oncoprotein shares functional similarities with such proteins as adenovirus E1A and SV40 large tumor antigen. As one of only two viral proteins always expressed in HPV-associated cancers, E7 plays a central role in both the viral life cycle and carcinogenic transformation. In the HPV viral life cycle, E7 disrupts the intimate association between cellular differentiation and proliferation in normal epithelium, allowing for viral replication in cells that would no longer be in the dividing population. This function is directly reflected in the transforming activities of E7, including tumor initiation and induction of genomic instability. 相似文献