HUMAN PAPILLOMAVIRUS TYPE-16 ALTERS HUMAN EPITHELIAL-CELL DIFFERENTIATION INVITRO

HUMAN PAPILLOMAVIRUS TYPE-16 ALTERS HUMAN EPITHELIAL-CELL DIFFERENTIATION INVITRO
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DOI:
10.1073/pnas.85.19.7169
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发表时间:
1988-10-01
影响因子:
11.1
通讯作者:
LAIMINS, LA
LAIMINS, LA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MCCANCE, DJ;KOPAN, R;LAIMINS, LA

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人乳头瘤病毒(HPV)16、18、31和33型被认为是宫颈癌和阴茎癌的病原体。使用角质形成细胞的细胞培养系统,允许分层和生产分化特异性角蛋白,我们已经研究了这些病毒之一,HPV-16,对人类上皮细胞的分化能力的影响。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SCC-13细胞(一种永生化鳞状细胞癌细胞系)中。克隆的新霉素耐药细胞系的分离和检查细胞培养提出的胶原筏。含有HPV-16 DNA的细胞系保留了在筏系统中分层和表达分化特异性角蛋白的能力,但在其他方面未能正常分化。HPV-16诱导的组织学异常与体内生殖器上皮内瘤变中观察到的组织学异常非常相似。因此,我们的研究结果支持HPV-16作为病原体在生殖器肿瘤的发展中的作用,并提出了一个特定的系统用于研究HPV-16诱导的上皮癌。
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.