title: Defective 3A trophoblast-endometrial cell adhesion and altered 3A growth and survival by human papillomavirus type 16 oncogenes.
abstract: Human papillomaviruses (HPVs) are found in trophoblasts of spontaneous abortions and replicate in these cells in culture. We used recombinant adeno-associated viruses (rAAV) to introduce the HPV-16 E6 and E7 oncogenes into 3A trophoblasts. AAV/E7/Neo-infected 3A trophoblasts died rapidly, but AAV/E6/Neo- and AAV/E6-E7/Neo-infected cells grew more rapidly than AAV/Neo-infected 3A cells and parental 3A. After G418 selection, the resulting E6-E7/3A and E6/3A cell lines were found to be highly defective for binding RL95 and HEC endometrial cells compared to Neo/3A and parental 3A. Serum requirements and soft agar colony formation analysis showed that E6-E7/3A had the most malignant phenotype, followed by E6/3A, with parental 3A cells having the lowest. E6/3A and E6-E7/3A were also immortal. Thus, HPV-16 oncogene expression may lead to outright trophoblast death, defective endometrial cell recognition, or a malignant phenotype. Any of these changes might lead to disruption/dysfunction of the trophoblast layer/gestational loss.
authors.affiliation: Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Carey
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Lowery
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hermonat
mesh_terms: D017209:Apoptosis; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000494:pharmacology*; D010641:Phenotype; D012097:Repressor Proteins; D014161:Transduction, Genetic; D014327:Trophoblasts / Q000378:metabolism / Q000821:virology*
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins