title: Activation of the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway in human cholesteatoma epithelium.
abstract: 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-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/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-κB 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-κB 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-κB, NF-κB 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-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.
authors: Department of Otolaryngology-Head and Neck Surgery, Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Hunan, 410011, Changsha, China.
authors: Wei
authors: W
authors: Liu
authors: Tuanfang
authors: T
authors: Yin
authors: Jihao
authors: J
authors: Ren
authors: Lihua
authors: L
authors: Li
authors: Zian
authors: Z
authors: Xiao
authors: Xing
authors: X
authors: Chen
authors: Dinghua
authors: D
authors: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002470:Cell Survival; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D004424:Ear Canal; D004848:Epithelium; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D055815:Young Adult
chemical_list: C530104:CCND1 protein, human; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt