Downstream Signal Transduction Pathway in Human Middle Ear Cholesteatoma
OBJECTIVES: Human cholesteatoma in the middle ear is characterized by the presence of a keratinized epithelium which is believed to have the hyperproliferative property. The pathogenesis of cholesteatoma including its hyperproliferative characteristic is still unknown. The proliferation and differentiation of cells in specialized tissues and the expression of their properties are under the control of a large number of regulatory processes and complex interactions called signal transduction. The signal transduction pathway may be initiated by the external signals such as growth factors which bind to their receptors and activate tyrosine kinases in the plasma membrane. With the development of the techniques of cell and molecular biologies, there have been many efforts to find the causes and to examine the biologic behaviors of the cholesteatoma. This study was undertaken to investigate the distribution of PLC-γ1, EGFR, PI3K and PDGFR in human middle ear cholesteatoma. MATERIALS AND METHODS: Using Western blot, RT-PCR and immunohistochemical techniques, we investigated the reaction patterns of antibodies to PLC-γ1, EGFR, PDGFR-α, PDGFR-β, and PI3K as the proliferation and differentiation markers in 10 human middle ear cholesteatoma specimens. For the control, same study was performed with retroauricular skin. RESULTS: In RT-PCR, EGFR, PDGFR-β, and PLC-γ1 were detected in cholesteatoma epitheliums, while PDGFR-α and PI3K were not detected. Only PDGFR-β was detected in retroauricular skins. In immunostaining, intensity of PDGFR-α and PI3K were not expressed in cholesteatoma epitheliums and retroauricular skins. EGFR protein was detectable in both basal cell and the suprabasal cell layers of cholesteatoma epitheliums, while it was detectable only in the basal cell layer of retroauricular skins. Strong expression of PDGFR-β was detected in some cholesteatoma epitheliums, while it was detected weakly in retroauricular skins. Expression of PLC-γ1 at the suprabasal cell layer and basal cell layer were more intense in cholesteatoma epitheliums than that in retroauricular skins. Using Western blot, EGFR and PLC-γ1 were detected strongly in cholesteatoma epitheliums than in the retroauricular skins, while PDGFR-β was detected strongly in retroauricular skins than in the cholesteatoma epitheliums. CONCLUSION: In human middle ear cholesteatomas, the role of downstream signal transduction pathway through EGFR and PLC-γ1 seemed to be dominant for the proliferation and differentiation of the keratinocyte.
중이 진주종, 신호전달 체계, 면역조직화학적 염색, Cholesteatoma, RT-PCR, Western blot, downstream signal transduction pathway, immunohistochemical staining
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