title: Temporal and histologic relationships of proliferating cell nuclear antigen and human papillomavirus type 11 in the mouse xenograft system.
abstract: Proliferating cell nuclear antigen (PCNA) is an accessory protein of DNA polymerase delta. This protein is associated with cell cycle progression and can be detected in the replicating cells of normal tissues. Condylomata acuminata are benign epithelial tumors caused by infection with human papillomaviruses and are characterized by abnormal cell proliferation. The athymic mouse xenograft model of HPV 11 infection was used to test the hypothesis that PCNA is induced early in the course of HPV 11 infection and to study the temporal and histologic relationships between detection of PCNA and HPV DNA. Human foreskin tissue was infected with HPV 11 and implanted under the renal capsules of 10 athymic mice. Pairs of mice were sacrificed every week beginning four weeks after implantation. HPV DNA was detected in sections of foreskin implants by in situ hybridization. PCNA was as or more abundant in implants removed at earlier time points than at later time points, whereas HPV DNA became increasingly more abundant with time. PCNA was detected only in basal cells in areas of histologically normal epithelium that were also negative for HPV DNA. In contrast, PCNA was present throughout the epithelium in regions that were HPV DNA-positive. HPV DNA was detected only in differentiated epithelial cells in implants removed at all five time points, but in HPV DNA-positive regions, PCNA was detected with equal intensity in differentiated and undifferentiated cells. The foci of PCNA-positive cells were well demarcated and were larger than, but included, the foci of HPV DNA-positive cells. PCNA may be induced maximally in differentiated epithelium by HPV 11 prior to significant HPV DNA replication.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Brown
authors.forename: L
authors.initials: L
authors.lastname: Pratt
authors.forename: K H
authors.initials: KH
authors.lastname: Fife
authors.forename: J T
authors.initials: JT
authors.lastname: Bryan
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003218:Condylomata Acuminata / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics*; D004195:Disease Models, Animal; D004848:Epithelium; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology*; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D004279:DNA, Viral; D018809:Proliferating Cell Nuclear Antigen