Winter Jochen, Pantelis Annette, Allam Jean-Pierre, Novak Natalija, Reich Rudolf, Martini Markus, Bergé Stefaan, Deschner James, Jepsen Soeren, Wenghoefer Matthias
Department of Periodontology, University of Bonn, Germany.
J Craniofac Surg. 2011 Jan;22(1):100-4. doi: 10.1097/SCS.0b013e3181f6c5e9.
The purposes of this study were to analyze the gene expression pattern of antimicrobial peptides, tumor suppressors, growth factors, matrix metalloproteases, and inflammatory cytokines and chemokines in oral irritation fibromas and to identify genes with protective effects against malignant transformation in benign proliferating tumors of the oral mucosa.
Biopsies of irritation fibromas (n = 15) and healthy gingiva (n = 15) were obtained during routine surgical procedures. RNA was extracted according to standard protocols, and transcription levels of CCL20, DEFA 1/3, DEFA 4, S100A7, DOC-1, interleukin (IL) 1β, IL-6, IL-8, IL-10, tumor necrosis factor α, Cox-2, matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-8, MMP-9, transforming growth factor β1, transforming growth factor α, and keratinocyte growth factor were analyzed by real-time polymerase chain reaction. In addition, immunostaining was performed to visualize the transcription products of the genes of interest in fibroma tissue as well as in healthy gingiva.
The gene expression of S100A7 was 11.3-fold and that of DEFA 1/3 was 14-fold higher in irritation fibromas than in healthy gingiva, whereas the expression of MMP-3 and of inflammation markers IL-1β, IL-6, IL-8, tumor necrosis factor α, and Cox-2 was reduced. Profound down-regulation of DOC-1 gene expression, characteristic for proliferating malignant tumors of the oral cavity, was in irritation fibromas not verifiable.
Changes in the expression pattern of S100A7, DEFA 1/3, and MMP-3 seem to be involved in the development of irritation fibromas, whereas chronic inflammation might be of less importance. Overexpression of S100A7, but missing down-regulation of the tumor-suppressor gene DOC-1, might exert protective effects and counteract malignant transformation of benign, proliferating lesions of the oral cavity.
本研究旨在分析口腔刺激纤维瘤中抗菌肽、肿瘤抑制因子、生长因子、基质金属蛋白酶以及炎性细胞因子和趋化因子的基因表达模式，并确定在口腔黏膜良性增殖性肿瘤中具有抗恶性转化保护作用的基因。
在常规外科手术过程中获取刺激纤维瘤（n = 15）和健康牙龈（n = 15）的活检组织。按照标准方案提取RNA，并通过实时聚合酶链反应分析CCL20、DEFA 1/3、DEFA 4、S100A7、DOC-1、白细胞介素（IL）1β、IL-6、IL-8、IL-10、肿瘤坏死因子α、Cox-2、基质金属蛋白酶1（MMP-1）、MMP-2、MMP-3、MMP-8、MMP-9、转化生长因子β1、转化生长因子α和角质形成细胞生长因子的转录水平。此外，进行免疫染色以观察纤维瘤组织以及健康牙龈中感兴趣基因的转录产物。
刺激纤维瘤中S100A7的基因表达比健康牙龈高11.3倍，DEFA 1/3的基因表达高14倍，而MMP-3以及炎症标志物IL-1β、IL-6、IL-8、肿瘤坏死因子α和Cox-2的表达降低。口腔增殖性恶性肿瘤特有的DOC-1基因表达的显著下调在刺激纤维瘤中未得到证实。
S100A7、DEFA 1/3和MMP-3表达模式的变化似乎与刺激纤维瘤的发生有关，而慢性炎症可能不太重要。S100A7的过表达，但肿瘤抑制基因DOC-1未下调，可能发挥保护作用并抵消口腔良性增殖性病变的恶性转化。
