title: Human papillomavirus type 16 alters human epithelial cell differentiation in vitro.
abstract: 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.
authors: Howard Hughes Medical Institute, University of Chicago, IL 60637.
authors: D J
authors: DJ
authors: McCance
authors: R
authors: R
authors: Kopan
authors: E
authors: E
authors: Fuchs
authors: L A
authors: LA
authors: Laimins
mesh_terms: D015139:Blotting, Southern; D002454:Cell Differentiation; D002460:Cell Line; D000078404:Epidermal Cells; D005260:Female; D006801:Humans; D007633:Keratins; D008297:Male; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D010412:Penile Neoplasms / Q000382:microbiology; D011230:Precancerous Conditions / Q000382:microbiology; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000382:microbiology
chemical_list: D007633:Keratins