Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia.
OBJECTIVE
The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva.


METHODS
Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of alpha-defensin (DEFA) 1/3, DEFA-4, S100-A7, deleted-in-oral-cancer (Doc) 1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF) alpha, cyclooxygenase (Cox) 2, epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor (TGF) beta1, TGF-alpha, collagen-IA1 (Col-1), and tenascin-c were analyzed by real-time reverse-transcription polymerase chain reaction. The proteins encoded by the different genes were visualized by immunostaining.


RESULTS
Compared with healthy gingiva (set as 1), there was an increased gene expression of DEFA-4 (179.2-fold), S100-A7 (25.4-fold), EGF (24.8-fold), TGF-beta1 (25.2-fold), and tenascin-c (34.3-fold) in oral leukoplakia. The expression of IL-1beta and Doc-1 was decreased (0.01-fold and 0.2-fold, respectively).


CONCLUSIONS
The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, EGF, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. Chronic inflammation seems not to be involved in the development of this lesion.
Wenghoefer
M
M
Department of Oral and Maxillofacial Plastic Surgery, University of Bonn, Bonn, Germany.
Pantelis
A
A
Najafi
T
T
Deschner
J
J
Allam
J P
JP
Novak
N
N
Reich
R
R
Martini
M
M
Bergé
S
S
Fischer
H P
HP
Jepsen
S
S
Winter
J
J
D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005881:Gingiva / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007972:Leukoplakia, Oral / Q000276:immunology / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D012016:Reference Values; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism
C096151:CDK2AP1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007378:Interleukins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D019063:Tenascin; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D023084:alpha-Defensins; D051523:Fibroblast Growth Factor 7; D004815:Epidermal Growth Factor; D012313:RNA; D051546:Cyclooxygenase 2