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学科主题: 临床医学
题名:
Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix
作者: Zhang, AJ; Wang, JL; Zheng, BY; Fang, XL; Angstrom, T; Liu, C; Li, XD; Erlandsson, F; Bjorkholm, M; Nordenskjord, M; Gruber, A; Wallin, KL; Xu, DW
关键词: cervical cancer ; HPV ; genomic instability ; telomere erosion ; telomerase
刊名: ONCOGENE
发表日期: 2004-09-23
DOI: 10.1038/sj.onc.1207527
卷: 23, 期:44, 页:7441-7447
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: SQUAMOUS INTRAEPITHELIAL LESIONS ; HUMAN-PAPILLOMAVIRUS TYPE-16 ; COMPARATIVE GENOMIC HYBRIDIZATION ; REVERSE-TRANSCRIPTASE GENE ; HTERT GENE ; CHROMOSOME INSTABILITY ; HUMAN CANCER ; AMPLIFICATION ; DYSFUNCTION ; ACTIVATION
英文摘要:

Although human papillomavirus (HPV) has been defined as the pathogen for cervical carcinomas, molecular events underlying the oncogenic process are unclear. As telomere dysfunction-mediated chromosomal instability and telomerase activation have been suggested as key events in carcinogenesis, we dissected the dynamic changes in telomere length, checkpoint response, and temporal pro. le of telomerase expression during the evolution from precursor lesions ( cervical intraepithelial neoplasia, CINs) to invasive cancers of the uterine cervix in sequential samples from 16 patients. Telomeres were significantly shortened in all CIN samples and no further substantial attritions occurred in most cases with the acquisition of malignant phenotype. Very short telomeres were coupled with constitutive activation of the DNA damage response pathway (Chk2 phosphorylation) and increased cellular proliferation in those cervical specimens. Telomerase reverse transcriptase ( hTERT) expression was preferably induced at advanced CINs or invasive cancers. The present finding demonstrates that excessive telomere shortening predominantly occurs in the early carcinogenesis of the uterine cervix largely prior to telomerase activation. Widespread over-erosion of telomeres or telomere dysfunction in very early stages of cervical tumorigenesis might fuel transformation processes by driving chromosomal instability.

语种: 英语
WOS记录号: WOS:000224021400015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55690
Appears in Collections:北京大学第二临床医学院_妇科_期刊论文

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作者单位: 1.Univ Umea Hosp, Cytol Lab, SE-90187 Umea, Sweden
2.Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med, CMM, SE-17176 Stockholm, Sweden
3.Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden
4.Karolinska Univ Hosp, Karolinska Inst, Dept Pathol & Oncol, SE-17176 Stockholm, Sweden
5.Peking Univ, Peoples Hosp, Dept Gynecol, Beijing 100083, Peoples R China
6.Shandong Univ, Qilu Hosp, Dept Urol, Jinan 250108, Peoples R China
7.Karolinska Univ Hosp, Karolinska Inst, Dept Urol, SE-17176 Stockholm, Sweden

Recommended Citation:
Zhang, AJ,Wang, JL,Zheng, BY,et al. Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix[J]. ONCOGENE,2004,23(44):7441-7447.
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