title: Upregulation of phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in acquired middle ear cholesteatoma growth.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan. kuyaho@kmu.edu.tw
authors.forename: Kuen Yao
authors.initials: KY
authors.lastname: Ho
authors.forename: Tai Sheng
authors.initials: TS
authors.lastname: Yeh
authors.forename: Han Hsiang
authors.initials: HH
authors.lastname: Huang
authors.forename: Kuo Feng
authors.initials: KF
authors.lastname: Hung
authors.forename: Chee Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Wan Tzu
authors.initials: WT
authors.lastname: Chen
authors.forename: Shih Meng
authors.initials: SM
authors.lastname: Tsai
authors.forename: Ning Chia
authors.initials: NC
authors.lastname: Chang
authors.forename: Chen Yu
authors.initials: CY
authors.lastname: Chien
authors.forename: Hsun Mo
authors.initials: HM
authors.lastname: Wang
authors.forename: Yu Jen
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D054464:Peroxiredoxins / Q000378:metabolism*; D010766:Phosphorylation; D012867:Skin / Q000378:metabolism / Q000473:pathology; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; C086065:PRDX2 protein, human; D054464:Peroxiredoxins