Identification of Id1 in acquired middle ear cholesteatoma.
OBJECTIVE
To determine (1) the relationship between chronic inflammatory changes in the ossicular chain area (OCA) and the formation of cholesteatoma and (2) the correlates between aberrant gene expression and abnormal proliferation of cholesteatoma.


METHODS
Two hundred sixty-four ears with chronic otitis media that had undergone ear surgery were included in this study for statistical analysis of the relationship between abnormalities in the OCA and cholesteatoma. Fourteen middle ear cholesteatoma specimens were collected for immunohistochemical analysis of candidate molecules involved in the abnormal proliferation of keratinocytes. A cell model was used for verification of candidate molecule involvement.


RESULTS
The formation of cholesteatoma was accompanied by chronic inflammatory changes in the OCA, including granulated tissue, adhesion, and stagnating effusion. The inhibitor of the DNA-binding (Id1) gene, which is involved in controlling cell cycle progression, was abundantly expressed in cholesteatoma epithelium. In vitro studies indicate that Id1 regulated the expression of nuclear factor kappaB, cyclin D1, proliferating cell nuclear antigen, and cell cycle progression of keratinocytes,


CONCLUSIONS
Chronic inflammation in the OCA is closely related to the formation of cholesteatoma. The Id1/nuclear factor kappaB/cyclin D1/proliferating cell nuclear antigen signaling pathway is involved in the abnormal proliferation of keratinocytes in acquired cholesteatoma.
Zhang
Quan-An
QA
Department of Otolaryngology, Xi'an Jiao University, Xi'an, People's Republic of China.
Hamajima
Yuki
Y
Zhang
Qing
Q
Lin
Jizhen
J
D002453:Cell Cycle; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism* / Q000473:pathology; D004429:Ear Ossicles / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D014162:Transfection
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1