McCance D J, Kopan R, Fuchs E, Laimins L A
Howard Hughes Medical Institute, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1988 Oct;85(19):7169-73. doi: 10.1073/pnas.85.19.7169.
Human papillomavirus (HPV) types 16, 18, 31, and 33 have been implicated as etiologic agents of cervical and penile cancer. Using a cell culture system for keratinocytes which allows stratification and production of differentiation-specific keratins, we have examined the effects of one of these viruses, HPV-16, on the differentiation capabilities of human epithelial cells. A plasmid containing the HPV-16 genome and a neomycin-selectable marker was transfected into primary human epidermal cells and SCC-13 cells, an immortalized squamous cell carcinoma cell line. Cloned neomycin-resistant cell lines were isolated and examined by cell culture on raised collagen rafts. Cell lines containing HPV-16 DNA retained the ability to stratify and express differentiation-specific keratins in the raft system but otherwise failed to differentiate normally. The histological abnormalities induced by HPV-16 closely resembled those seen in genital intraepithelial neoplasia in vivo. Hence, our results support the role of HPV-16 as an etiologic agent in the development of genital neoplasias and suggest a specific system for the study of HPV-16-induced epithelial cancers.
人乳头瘤病毒16型、18型、31型和33型被认为是宫颈癌和阴茎癌的病原体。我们利用一种用于角质形成细胞的细胞培养系统，该系统允许分层并产生分化特异性角蛋白，研究了其中一种病毒HPV - 16对人上皮细胞分化能力的影响。将含有HPV - 16基因组和新霉素选择标记的质粒转染到原代人表皮细胞和永生化鳞状细胞癌细胞系SCC - 13细胞中。分离出克隆的新霉素抗性细胞系，并在升高的胶原筏上进行细胞培养检查。含有HPV - 16 DNA的细胞系在筏系统中保留了分层和表达分化特异性角蛋白的能力，但在其他方面无法正常分化。HPV - 16诱导的组织学异常与体内生殖器上皮内瘤变中所见的异常非常相似。因此，我们的结果支持HPV - 16作为生殖器肿瘤发生的病原体的作用，并提出了一个用于研究HPV - 16诱导的上皮癌的特定系统。
