Upregulation of Phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in Acquired Middle Ear Cholesteatoma Growth

International Journal of Molecular Sciences

Kuen Yao Ho¹  Tai Sheng Yeh⁶  Han Hsiang Huang⁵  Kuo Feng Hung³  Chee Yin Chai²  Wan Tzu Chen²  Shih Meng Tsai⁸  Ning Chia Chang⁴  Chen Yu Chien¹  Hsun Mo Wang⁷ 

[1] Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan; E-Mails:;Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan; E-Mails:;Graduate Institute of Applied Health and Biotechnology, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan; E-Mail:;Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Otorhinolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan; E-Mail:;Department of Public Health, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan; E-Mail:

关键词: cholesteatoma;    HSP27;    PRDX2;    GRP75;    GRP78;    GRP94;   

DOI  :  10.3390/ijms140714439

来源: mdpi

【 摘 要 】

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland