Mediation of signal transduction in keratinocytes of human middle ear cholesteatoma by ras protein.

Immunolocalization was used to investigate the distribution of ras protein in both congenital and acquired cholesteatoma tissues. A pathological feature of middle ear cholesteatoma included accumulation of keratin debris due to active proliferation and differentiation of keratinocytes. Ras protein localized to the inner plasma membrane and cytoplasm 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. Findings also demonstrated that receptors for epidermal growth factor, fibroblast growth factor, and plateletderived growth factor were present in the plasma membrane of keratinocytes. C-jun, a transcription factor was found in the nuclei of keratinocytes of the cholesteatoma epithelium. These findings indicate that ras protein plays a pivotal role in a signal transduction cascade between growth factor receptors in the plasma membrane and the transcription factor, c-jun, in the nuclei of keratinocytes during the growth of cholesteatoma.