title: Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic adenomas of salivary glands.
abstract: Although antimicrobial peptides (AMPs) appear to have diverse functional activities in innate immunity, a few reports suggest a potential role of human beta-defensin (hBD)-1 in tumor suppression. The aim of the present study was to compare the expression patterns of hBD-1, -2 and -3 in various features of human salivary gland tissues, such as healthy parenchyma, chronic sialadenitis and intraglandular pleomorphic adenomas, with their adjacent normal tissues. Twenty human salivary gland specimens (five healthy, five chronic sialadenitis, five pleomorphic adenomas and five adenoma adjacent normal tissues (AANTs)) were investigated for mRNA expression levels of hBD-1, -2 and -3 by quantitative real-time RT-PCR. Additionally, immunohistochemistry for the hBD-1, -2 and -3 peptides was performed for analysis of localization. Considerably increased, 80-fold higher hBD-1 and increased hBD-3 mRNA expression levels compared to healthy salivary gland tissues were detected in chronic sialadenitis. In pleomorphic adenomas hBD-2 expression levels were lower, but hBD-1 expression levels were significant decreased (p=0.03) compared to healthy parenchyma. Interestingly, the AANTs showed a 48-fold higher expression of hBD-1 and increased hBD-3 expression compared to the healthy salivary gland. Immunohistochemistry of the tumors showed nuclear hBD-1 localization. For the first time, it was shown that hBD-1 gene expression is significantly decreased in pleomorphic adenomas, while simultaneously the protein is localized in the nucleus. Increased expression levels in glandular inflammation have been described previously albeit not in AANTs. These data support the hypothesis that hBD-1 might be a potential tumor suppressor also in benign salivary gland tumors in addition to other genetic alterations.
authors.affiliation: Department of Otorhinolaryngology/Surgery, University of Bonn, D-53105 Bonn, Germany. annette.pantelis@ukb.uni-bonn.de
authors.forename: Annette
authors.initials: A
authors.lastname: Pantelis
authors.forename: Matthias
authors.initials: M
authors.lastname: Wenghoefer
authors.forename: Susanne
authors.initials: S
authors.lastname: Haas
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pantelis
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.forename: Jochen
authors.initials: J
authors.lastname: Winter
mesh_terms: D008949:Adenoma, Pleomorphic / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D012793:Sialadenitis / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D023083:beta-Defensins