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Notch Signaling in Acquired Middle Ear Cholesteatoma

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Title: Notch Signaling in Acquired Middle Ear Cholesteatoma
Authors: Fukuda, Atsushi Browse this author
Kano, Satoshi Browse this author
Nakamaru, Yuji Browse this author
Morita, Shinya Browse this author
Hoshino, Kimiko Browse this author
Fujiwara, Keishi Browse this author
Homma, Akihiro Browse this author →KAKEN DB
Keywords: Cholesteatoma
Notch signaling
Issue Date: Oct-2021
Publisher: Lippincott Williams & Wilkins (LWW)
Journal Title: Otology & neurotology
Volume: 42
Issue: 9
Start Page: E1389
End Page: E1395
Publisher DOI: 10.1097/MAO.0000000000003245
Abstract: Hypothesis: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. Background: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. Methods: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler (TM) PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. Results: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 +/- 32.4% and 44.9 +/- 17.8%, respectively) were significantly lower than in the EAC skin (83.4 +/- 17.5% and 55.7 +/- 7.1%, respectively) (p p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 +/- 11.4%) was significantly higher than in the EAC skin (0.5 +/- 0.7%) (p < 0.001). Conclusion: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.
Rights: This is a non-final version of an article published in final form in Fukuda, Atsushi; Kano, Satoshi; Nakamaru, Yuji; Morita, Shinya; Hoshino, Kimiko; Fujiwara, Keishi; Homma, Akihiro Notch Signaling in Acquired Middle Ear Cholesteatoma, Otology & Neurotology: October 2021 Volume 42 Issue 9 p e1389-e1395
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 本間 明宏

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