{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:13:54Z","timestamp":1788261234462,"version":"build-2803163510"},"reference-count":35,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Hunan Provincial Innovation Foundation For Postgraduate, China","award":["CX2010B055"],"award-info":[{"award-number":["CX2010B055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore,<jats:italic>in vitro<\/jats:italic>studies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR\/PI3K\/Akt\/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR\/PI3K\/Akt\/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR\/PI3K\/Akt\/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma.<\/jats:p>","DOI":"10.1155\/2013\/651207","type":"journal-article","created":{"date-parts":[[2013,11,7]],"date-time":"2013-11-07T16:02:20Z","timestamp":1383840140000},"page":"1-9","source":"Crossref","is-referenced-by-count":32,"title":["The Role of EGFR\/PI3K\/Akt\/cyclinD1 Signaling Pathway in Acquired Middle Ear Cholesteatoma"],"prefix":"10.1155","volume":"2013","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmiao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, 139 Middle 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