Microarrayanalysisidentifiesdifferentiation-associated：微阵列分析确定分化有关的.pdfVIP

Available online at R Virology 314 (2003) 196–205 /locate/yviro Microarray analysis identifies differentiation-associated genes regulated by human papillomavirus type 16 E6 Carol L. Duffy, Stacia L. Phillips, and Aloysius J. Klingelhutz* Department of Microbiology and Holden Cancer Center, University of Iowa, 2202 MEBRF, 375 Newton Road, Iowa City, IA 52242, USA Received 18 February 2003; returned to author for revision 20 March 2003; accepted 30 April 2003 Abstract In this study, we used oligonucleotide microarray analysis to determine which cellular genes are regulated by the human papillomavirus type 16 (HPV-16) E6 oncoprotein. We found that E6 causes the downregulation of a large number of cellular genes involved in keratinocyte differentiation, including genes such as small proline-rich proteins, transglutaminase, involucrin, elafin, and cytokeratins, which are normally involved in the production of the cornified cell envelope. In contrast, E6 upregulates several genes, such as vimentin, that are usually expressed in mesenchymal lineages. E6 also modulates levels of genes involved in inflammation, including Cox-1 and Nag-1. By using E6 mutants that differentially target p53 for degradation, we determined that E6 regulates cellular genes by both p53-dependent and independent mechanisms. The microarray data also indicate that HPV-16 E6 modulates certain effects of HPV-16 E7 on cellular gene expression. The identification of E6-regulated genes in this analysis provides a basis for further studies on their role in HPV infection and cellular transformation. © 2003 Elsevier Science (USA). All rights reserved. Keywords: Human papillomav