The role of inhibitor of DNA-binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media.

Abstract

OBJECTIVES:

A hallmark of cholesteatoma is hyperproliferation of keratinocytes with abundant production of keratins in the middle ear under chronic inflammatory conditions. However, little is known about the driving force of cellular proliferation and keratin production of cholesteatomal matrix. The purpose of this study was to investigate the cellular proliferation and keratin production of keratinocytes under the influence of Id1, a candidate transcription factor to cell proliferation.

MATERIALS AND METHODS:

Keratinocytes were transfected with Id1 and the responses of keratinocytes to Id1 were studied by using cellular and molecular biologic methods.

RESULTS:

Id1 positively contributed to the cell cycle progression and negatively to the p16(Ink4a) downregulation via the nuclear factor-kappa B (NF-κB)/cyclin D1 pathway. Id1 significantly increased the promoter activity of NF-κB which, in turn, up-regulated the expression of cyclin D1 and keratin 10 in keratinocytes. Specific NF-κB inhibitors (pyrrolidine dithiocarbamate, PDTC), or dominant-negative inhibitor (I kappa B alpha mutant, IκBαM) abrogated the Id1-induced cell proliferation and keratin 10 production whereas p65, a subunit of the NF-κB heterodimer and an enhancer of the NF-κB activity, strengthened the Id1-induced cell proliferation and keratin 10 production.

CONCLUSIONS:

Id1 contributed to hyperproliferation of keratinocytes via enhancement of cell cycle progression, removal of cell cycle inhibition, and simultaneously increased keratin production.

• Authors: Y Hamajima, M Komori, D A Preciado, D I Choo, K Moribe, S Murakami, F G Ondrey, J Lin
• Journal: Cell proliferation (Cell Prolif) Vol. 43 Issue 5 Pg. 457-63 (Oct 2010) ISSN: 1365-2184 [Electronic] England
• PMID: 20887552 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• ID1 protein, human
• Inhibitor of Differentiation Protein 1
• Ki-67 Antigen
• NF-kappa B
• Cyclin D1
• Keratin-10

Topics

• Cell Line
• Cell Proliferation
• Cholesteatoma, Middle Ear (metabolism)
• Cyclin D1 (genetics, metabolism)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics, metabolism)
• Down-Regulation
• Humans
• Inhibitor of Differentiation Protein 1 (genetics, metabolism)
• Keratin-10 (genetics, metabolism)
• Keratinocytes (cytology)
• Ki-67 Antigen (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Otitis Media (metabolism)
• Transfection
• Up-Regulation