Factor by a Decrease in Epithelial Differentiation Growth Factor Receptor and Respond to Epidermal Growth Laryngeal Papilloma Cells Have High Levels of Epidermal

Laryngeal papillomas are benign epithelial tumors caused by human papillomaviruses. These tumors are characterized by hyperplasia of the spinous layer and abnormal differentiation. Many tumor cell lines overexpress the epidermal growth factor (EGF) receptor on their surface, and EGF regulates normal cell growth. We have asked about the relationship of the EGF receptor and EGF response in laryngeal papilloma cells. Papilloma cells showed markedly greater immunohistochemical staining for the EGF receptor, compared to uninfected cells. Both cell types showed a 2-3-fold increase in nuclei incorporating bromodeoxyuridine when EGF was present. Removal of EGF from papilloma cells cultured on collagen rafts permitted normal stratification and differentiation, as determined by synthesis of keratin 13. Inclusion of EGF induced abnormal differentiation with minimal expression of keratin 13. Uninfected laryngeal cells cultured on rafts in the presence of EGF synthesize keratin 13 in all suprabasal cells. EGF reduced both human papillomavirus RNA levels in the papil loma cells and expression of a reporter gene linked to the human papil lomavirus 11 enhancers and E6 promoter in uninfected cells. These results suggest that the phenotype of papillomas is induced, in part, by EGF binding to the abundant EGF receptors.