Suprabasal overexpression of beta-1 integrin is induced by bovine papillomavirus type 1.
In a normal stratified squamous epithelium, beta1-integrin is expressed in basal epithelial cells. In BPV-induced fibropapillomas beta1-integrin is overexpressed and aberrantly localized, with uniform expression in the lower spinous layer, and sporadic expression within the mid-spinous region that co-localizes with expression of the viral E5 and E7 oncoproteins. In situ hybridization of fibropapillomas for beta1-integrin RNA revealed sporadic hybridization in the spinous layer, indicating transcriptional induction. Beta1-integrin expression in cultured keratinocytes requires exogenous EGF in the media, but this requirement is lost if E7 is expressed, and E7 was able to abrogate the EGF-requirement of normal keratinocytes for the activation of ERK and DNA synthesis. Within fibropapillomas, suprabasal expression of E5 and E7 correlated with suprabasal expression of beta1-integrin and PCNA, indicating that vegetative viral replication in the spinous layer correlated with the expression of E7 and beta1 integrin. The ability of BPV-1 E7 to support beta1-integrin expression and EGF independent DNA synthesis and the activation of ERK are the first biochemical correlates of its expression in keratinocytes.
Cooper
Brooke
B
Institute of Pathology, Case Western Reserve University, 10900 Euclid Av., Cleveland, OH 44106, USA.
Brimer
Nicole
N
Stoler
Mark
M
Vande Pol
Scott B
SB
D000818:Animals; D015153:Blotting, Western; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000821:virology; D048748:MAP Kinase Kinase Kinase 3 / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000502:physiology*; D010212:Papilloma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication
D019012:Integrin beta1; D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; C075621:oncogene protein E7, Bovine papillomavirus type 1; D012313:RNA; D004247:DNA; D048748:MAP Kinase Kinase Kinase 3