The epithelial-mesenchymal transition induced by keratinocyte growth conditions is overcome by E6 and E7 from HPV16, but not HPV8 and HPV38: characterization of global transcription profiles.
The aim of this study was to evaluate the growth properties of primary human keratinocytes expressing E6 and E7 proteins, which are from either the beta- or alpha-genotypes, under different culture conditions. We demonstrated that keratinocytes expressing E6 and E7, from both HPV8 and 38, irreversibly underwent the epithelial-mesenchymal transition (EMT) when grown on plastic with FAD medium (F12/DMEM/5%FBS). Expression of E6/E7 from HPV16 was capable of fully overcoming the FAD-induced EMT. Immortalization was only observed in HPV16-transduced cell lines, while the more proliferating phenotype of both KerHPV8 and 38 was mainly related to FAD-induced EMT. Microarray analysis of exponentially growing cells identified 146 cellular genes that were differentially regulated in HPV16 compared to HPV8- and 38-transduced cells. A large accumulation of transcripts associated with epidermal development and differentiation was observed in HPV16-transduced cells, whereas transcripts of genes involved in the extracellular matrix, multicellular organismal processes, and inflammatory response were affected in HPV8 and 38-transduced cells.
Azzimonti
Barbara
B
Department of Clinical and Experimental Medicine, Medical School of Novara, via Solaroli 17, 28100 Novara, Italy.
Dell'oste
Valentina
V
Borgogna
Cinzia
C
Mondini
Michele
M
Gugliesi
Francesca
F
De Andrea
Marco
M
Chiorino
Giovanna
G
Scatolini
Maria
M
Ghimenti
Chiara
C
Landolfo
Santo
S
Gariglio
Marisa
M
D002454:Cell Differentiation / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D002478:Cells, Cultured / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008648:Mesoderm / Q000166:cytology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins