MEDIATION OF SIGNAL-TRANSDUCTION IN KERATINOCYTES OF HUMAN MIDDLE-EARCHOLESTEATOMA BY RAS PROTEIN

Immunolocalization was used to investigate the distribution of ras pro tein in both congenital and acquired cholesteatoma tissues. A patholog ical feature of middle ear cholesteatoma included accumulation of kera tin debris due to active proliferation and differentiation of keratino cytes. Ras protein localized to the inner plasma membrane and cytoplas m of keratinocytes in all of the epithelial layers in both congenital and acquired cholesteatoma specimens. Keratinocytes in the basal layer were stained more intensely than their differentiated counterparts. F indings also demonstrated that receptors for epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor were pres ent in the plasma membrane of keratinocytes. C-jun, a transcription fa ctor was found in the nuclei of keratinocytes of the cholesteatoma epi thelium. These findings indicate that ras protein plays a pivotal role in a signal transduction cascade between growth factor receptors in t he plasma membrane and the transcription factor, c-jun, in the nuclei of keratinocytes during the growth of cholesteatoma.