Suprabasal overexpression of Beta-1 integrin is induced by bovine papillomavirus type 1

In a normal stratified squamous epithelium, β1-integrin is expressed in basal epithelial cells. In BPV-induced fibropapillomas β1-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 β1-integrin RNA revealed sporadic hybridization in the spinous layer, indicating transcriptional induction. β1-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 β1-integrin and PCNA, indicating that vegetative viral replication in the spinous layer correlated with the expression of E7 and β1 integrin. The ability of BPV-1 E7 to support β1-integrin expression and EGF independent DNA synthesis and the activation of ERK are the first biochemical correlates of its expression in keratinocytes.