title: Enhanced StefinA and Sprr2 expression during papilloma formation in HPV8 transgenic mice.
abstract: BACKGROUND
  The human papillomavirus type 8 (HPV8) is associated with the development of non-melanoma skin cancer. Transgenic mice expressing the complete early gene region of HPV8 (E6/E7/E1/E2/E4=CER) or E6 separately under the control of the keratin14 promoter spontaneously developed papillomas characterized by varying degrees of epidermal dysplasia. Papilloma growth could be synchronized by a single UVA/B irradiation of the skin, which led to the development of papillomas within three weeks.
  
  
  OBJECTIVE
  The objective of this study was to identify alterations in cellular gene expression correlated with HPV8 oncogene expression in transgenic mice.
  
  
  METHODS
  We applied global gene expression profiling by microarray analysis and confirmed deregulation of cellular genes by qRT-PCR and immunohistochemical analysis.
  
  
  RESULTS
  By comparison of non-lesional HPV8-CER skin with skin of the parental mouse strain FVB/n, two cellular genes, namely StefinA and Sprr2, coding for precursor proteins of the cornified envelope, were predicted to be strongly upregulated in transgenic skin, which could be confirmed in subsequent qRT-PCR experiments. StefinA and Sprr2 mRNA expression was enhanced until day 7 after UV treatment with higher levels in HPV8 positive skin. While the expression of both genes returned to a normal level in the course of epidermis regeneration in wt mice, the expression persisted elevated in hyperplastic transgenic skin. Staining of an UV induced papilloma of FVB/n wt mouse revealed also strong expression of StefinA and Sprr2 indicating that upregulation in later stages of papilloma formation is independent of HPV8.
  
  
  CONCLUSIONS
  In non-lesional HPV8-CER transgenic skin StefinA and Sprr2 were found to be indirect/direct transcriptional targets of HPV8.
authors: Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany.
authors: Daliborka
authors: D
authors: Lazić
authors: Farnoosh
authors: F
authors: Alborzi
authors: Gian Paolo
authors: GP
authors: Marcuzzi
authors: Peter
authors: P
authors: Angel
authors: Jochen
authors: J
authors: Hess
authors: Herbert
authors: H
authors: Pfister
authors: Baki
authors: B
authors: Akgül
mesh_terms: D000818:Animals; D052686:Betapapillomavirus / Q000378:metabolism*; D055233:Cornified Envelope Proline-Rich Proteins / Q000096:biosynthesis*; D055312:Cystatin A / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D053547:Keratin-14 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010212:Papilloma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D055312:Cystatin A; D053547:Keratin-14; C491091:Sprr2a1 protein, mouse; C524995:Stfa1 protein, mouse