文章摘要信息

国际病理科学与临床杂志 2010, 30(1) 81- DOI: 10.3969/j.issn.16732588.2010. ISSN: 1673-2588 CN: 43-1458/R

本期目录 | 下期目录 | 过刊浏览 | 高级检索 [打印本页] [关闭]

综述

	扩展功能

	本文信息
	Supporting info
	PDF(970KB)
	[HTML全文]
	参考文献[PDF]
	参考文献
	服务与反馈
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	引用本文
	Email Alert
	文章反馈
	浏览反馈信息
	本文关键词相关文章
	人乳头瘤病毒
	宫颈癌
	E6
	E7
	本文作者相关文章
	PubMed

人乳头瘤病毒致癌机制的研究进展

冯松涛综述张志刚审校

复旦大学上海医学院病理学系，上海 200032

摘要：人乳头瘤病毒 (human papillomavirus, HPV) 是一类小双链DNA病毒，是世界范围内最常见的性传播病原体，其发现是肿瘤病因学研究中的重要成就之一。HPV仅感染人类上皮组织，根据组织亲嗜性的不同，可分为皮肤型和黏膜型；根据HPV致瘤性的高低，又可将黏膜型HPV分为低危型(low riskHPV, LRHPV)和高危型(high riskHPV, HRHPV)。LRHPV主要引起生殖器乳头状瘤和尖锐湿疣等良性病变，而HRHPV则主要引起宫颈不典型增生和宫颈癌。HRHPV可以通过基因整合及对宿主细胞基因组不稳定性、细胞周期、细胞凋亡以及端粒酶活性等产生影响等多种机制导致宫颈上皮的恶性转化。

关键词：人乳头瘤病毒宫颈癌 E6 E7

Progress in human papillomavirusinduced oncogenesis

FENG Songtao, ZHANG Zhigang

Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract: Human papillomavirus(HPV), a small doublestrand DNA virus, is the most common sexually transmitted causative agent in the world. The discovery of HPV is one of the most significant achievements in the etiology of oncology. HPV could be denominated as cutis or mucosa type dependent on the difference of epithelial tissues infected by HPV. The mucosa types could be further divided into high risk HPV and low risk HPV (LRHPV and HR HPV) based on the distinct pathogenesis. LRHPV infections cause a variety of benign proliferations like papillomas and warts of the genital tracts, while HRHPV infections lead to cervical dysplasia and invasive cervical cancer. HPV can mediate the malignant transformation of cervical epithelium through DNA integration and the effects on genome instability, cell cycle, apoptosis and telomerase activity.

Keywords: human papillomavirus;cervical cancer;E6;E7

收稿日期 2009-11-07 修回日期 2010-01-09 网络版发布日期

DOI: 10.3969/j.issn.16732588.2010.

基金项目:

通讯作者: 张志刚

作者简介:

作者Email: zzg@shmu.edu.cn

参考文献：

［1］Zur Hausen H. Papillomaviruses in the causation of human cancers-a brief historical account［J］. Virology, 2009, 384(2):260265. ［2］Steben M, DuarteFranco E. Human papillomavirus infection: epidemiology and pathophysiology［J］. Gynecol Oncol, 2007, 107(2 Suppl 1):S2S5. ［3］Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer［J］. N Engl J Med, 2003, 348(6):518527. ［4］Altekruse SF, Lacey JV Jr, Brinton LA, et al. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma［J］. Am J Obstet Gynecol, 2003, 188(3):657663. ［5］Pett M, Coleman N. Integration of highrisk human papillomavirus: a key event in cervical carcinogenesis?［J］. J Pathol, 2007, 212(4):356367. ［6］Vinokurova S, Wentzensen N, Kraus I, et al.Typedependent integration frequency of human papillomavirus genomes in cervical lesions［J］. Cancer Res, 2008, 68(1):307313. ［7］Wentzensen N, Vinokurova S, Doeberitz MV. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract［J］. Cancer Res, 2004, 64(11):38783884. ［8］Sheu BC, Chiou SH, Chang WC, et al. Integration of highrisk human papillomavirus DNA correlates with HLA genotype aberration and reduced HLA class I molecule expression in human cervical carcinoma［J］. Clin Immunol, 2005,115(3):295301. ［9］Duensing S, Münger K. Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins［J］. Int J Cancer, 2004, 109(2):157162. ［10］Guarguaglini G, Duncan PI, Stierhof YD, et al. The forkheadassociated domain protein Cep170 interacts with Pololike kinase 1 and serves as a marker for mature centrioles［J］. Mol Biol Cell, 2005, 16(3):10951107. ［11］Duensing S, Münger K. Centrosome abnormalities and genomic instability induced by human papillomavirus oncoproteins［J］. Prog Cell Cycle Res, 2003, 5:383391. ［12］Duensing S, Duensing A, Crum CP, et al. Human papillomavirus type 16 E7 oncoprotein induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype［J］. Cancer Res, 2001, 61(6):23562360. ［13］Boulet G, Horvath C, Vanden Broeck D,et al. Human papillomavirus: E6 and E7 oncogenes［J］. Int J Biochem Cell Biol, 2007, 39(11):20062011. ［14］Zimmermann H, Degenkolbe R, Bernard HU, et al. The human papillomavirus type 16 E6 oncoprotein can downregulate p53 activity by targeting the transcriptional coactivator CBP/p300［J］. J Virol, 1999, 73(8):62096219. ［15］Massimi P, Gammoh N, Thomas M, et al. HPV E6 specifically targets different cellular pools of its PDZ domaincontaining tumour suppressor substrates for proteasomemediated degradation［J］. Oncogene, 2004, 23(49):80338039. ［16］McLaughlinDrubin ME, Münger K. The human papillomavirus E7 oncoprotein［J］. Virology, 2009, 384(2):335344. ［17］McLaughlinDrubin ME, Huh KW, Munger K. Human papillomavirus type 16 E7 oncoprotein associates with E2F6［J］. J Virol, 2008, 82(17):86958705. ［18］Filippova M, Song H, Connolly JL, et al. The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNFinduced apoptosis［J］. J Biol Chem, 2002, 277(24):2173021739. ［19］James MA, Lee JH, Klingelhutz AJ. Human papillomavirus type 16 E6 activates NFkappa B, induces cIAP2 expression, and protects against apoptosis in a PDZ binding motifdependent manner［J］. J Virol, 2006, 80(11):53015307. ［20］Santer FR, Moser B, Spoden GA, et al. Human papillomavirus Type 16 E7 oncoprotein inhibits apoptosis mediated by nuclear insulinlike growth factorbinding protein3 by enhancing its ubiquitin/proteasomedependent degradation［J］. Carcinogenesis, 2007, 28(12):25112520. ［21］Severino A, Abbruzzese C, Manente L, et al. Human papillomavirus16 E7 interacts with Siva1 and modulates apoptosis in HaCaT human immortalized keratinocytes［J］. J Cell Physiol, 2007, 212(1):118125. ［22］Seewaldt VL, Mrozek K, Dietze EC, et al. Human papillomavirus type 16 E6 inactivation of p53 in normal human mammary epithelial cells promotes tamoxifenmediated apoptosis［J］. Cancer Res, 2001, 61(2):616624. ［23］Thyrell L, Sangfelt O, Zhivotovsky B, et al. The HPV16 E7 oncogene sensitizes malignant cells to IFNalphainduced apoptosis［J］. J Interferon Cytokine Res, 2005, 25(2):6372. ［24］Xu M, Luo W, Elzi DJ, et al. NFX1 interacts with mSin3A/histone deacetylase to repress hTERT transcription in keratinocytes［J］. Mol Cell Biol, 2008, 28(15):48194828. ［25］Lee D, Kim HZ, Jeong KW, et al. Human papillomavirus E2 downregulates the human telomerase reverse transcriptase promoter［J］. J Biol Chem, 2002, 277(31):2774827756. ［26］Madkan VK, CookNorris RH, Steadman MC, et al. The oncogenic potential of human papillomaviruses: a review on the role of host genetics and environmental cofactors［J］. Br J Dermatol, 2007, 157(2):228241. ［27］Delvenne P, Herman L, Kholod N, et al. Role of hormone cofactors in the human papillomavirusinduced carcinogenesis of the uterine cervix［J］. Mol Cell Endocrinol, 2007, 264(12):15. ［28］Stanley M. Prevention strategies against the human papillomavirus: the effectiveness of vaccination［J］. Gynecol Oncol, 2007, 107(2 Suppl 1):S19S23.

本刊中的类似文章

1．杨兰1;孙振柱2，李锋1 .HLA与HPV相关肿瘤的研究进展[J]. 国际病理科学与临床杂志, 2006,26(4): 12-324

2．曾源1，陈忠东1，曹建国2.8-硝基白杨素对人宫颈癌Hela细胞增殖和凋亡的影响[J]. 国际病理科学与临床杂志, 2007,27(2): 2-104

3．何慧娟综述沈琦审校.活性氧在宫颈癌形成中的作用[J]. 国际病理科学与临床杂志, 2009,29(5): 426-430