title: Upregulation of epidermal growth factor receptor 4 in oral leukoplakia.
abstract: In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tsurumi University, Yokohama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kumagai
authors.forename: Akito
authors.initials: A
authors.lastname: Gotoh
authors.forename: Takanori
authors.initials: T
authors.lastname: Eguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hamada
authors.forename: Satsuki
authors.initials: S
authors.lastname: Suzuki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D066258:Amphiregulin; D066259:Betacellulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism; D066260:Epiregulin; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D007972:Leukoplakia, Oral / Q000378:metabolism*; D017676:Lichen Planus, Oral / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009414:Nerve Growth Factors; D020880:Neuregulins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D011956:Receptors, Cell Surface / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D066258:Amphiregulin; D066259:Betacellulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor; D066260:Epiregulin; D066246:ErbB Receptors; D006023:Glycoproteins; D006493:Heparin; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009414:Nerve Growth Factors; D020880:Neuregulins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011956:Receptors, Cell Surface; D016211:Transforming Growth Factor alpha; C587848:AREG protein, human; C587851:BTC protein, human; C587880:EREG protein, human; C587883:HBEGF protein, human; C106766:NRG2 protein, human; C467747:neuregulin-4; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human