Akgül B, Lemme W, García-Escudero R, Storey A, Pfister H J
Institute of Virology and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Arch Virol. 2005 Jan;150(1):145-51. doi: 10.1007/s00705-004-0398-4. Epub 2004 Oct 5.
Human papillomaviruses (HPV) have been implicated in the development of non-melanoma skin cancer (NMSC). HPV types 5 and 8 are strongly associated with NMSC in patients with the inherited disease Epidermodysplasia verruciformis (Ev). In these patients tumours arise predominantly on sun-exposed skin and consistently harbour HPV DNAs. To determine whether UV-B irradiation modulates the noncoding region (NCR) promoter activity of the Ev-HPV types 5, 8, 9, 14, 23, 24, and 25 we performed transient transfection assays with NCR luciferase reporter gene constructs in primary human epithelial keratinocytes (PHEKs) and in p53-null RTS3b cells. Each of the HPVs showed different basal NCR activity in both cell types and reacted differently upon UVB treatment and p53 cotransfection in RTS3b cells. The NCR of HPV5 and 8 were the only ones to be activated by UV-B in PHEKs. The stimulation of the NCR activity of the high-risk cutaneous HPV types 5 and 8 by UV-B irradiation may point to a role of this interaction in the development of NMSC.
人乳头瘤病毒(HPV)与非黑素瘤皮肤癌(NMSC)的发生有关。5型和8型HPV与患有遗传性疾病疣状表皮发育不良(Ev)的患者的NMSC密切相关。在这些患者中,肿瘤主要发生在阳光暴露的皮肤上,并且始终含有HPV DNA。为了确定UV-B照射是否调节Ev-HPV 5、8、9、14、23、24和25型的非编码区(NCR)启动子活性,我们在原代人上皮角质形成细胞(PHEK)和p53缺失的RTS3b细胞中用NCR荧光素酶报告基因构建体进行了瞬时转染试验。每种HPV在两种细胞类型中均显示出不同的基础NCR活性,并且在RTS3b细胞中经UVB处理和p53共转染后反应不同。HPV5和8的NCR是PHEK中仅有的被UV-B激活的NCR。UV-B照射对高危皮肤HPV 5型和8型NCR活性的刺激可能表明这种相互作用在NMSC发生中的作用。