Activation of the EGFR/Akt/NF-kappa B/cyclinD1 survival signaling pathway in human cholesteatoma epithelium

作者:Liu, Wei; Yin, Tuanfang; Ren, Jihao*; Li, Lihua; Xiao, Zian; Chen, Xing; Xie, Dinghua
来源:European Archives of Oto-Rhino-Laryngology, 2014, 271(2): 265-273.
DOI:10.1007/s00405-013-2403-6

摘要

Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-kappa B)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-kappa B/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-kappa B and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-kappa B and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p < 0.01). In cholesteatoma epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-kappa B, NF-kappa B and cyclinD1, respectively (p < 0.01). No significant relationships were observed between the levels of investigated proteins and the degree of bone destruction (p > 0.05). The increased protein expression of p-EGFR, p-Akt, NF-kappa B and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-kappa B/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.