Kumamoto Hiroyuki, Ooya Kiyoshi
Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
J Oral Pathol Med. 2005 May;34(5):287-94. doi: 10.1111/j.1600-0714.2005.00311.x.
To clarify the roles of the apoptosis signaling pathway mediated by death receptors in oncogenesis and cytodifferentiation of odontogenic tumors, expression of tumor necrosis factor alpha (TNFalpha), TNF-related apoptosis-inducing ligand (TRAIL), and their associated molecules was analyzed in ameloblastomas as well as in tooth germs.
Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry to determine the expression of TNFalpha, TNF receptor I (TNFRI), TRAIL, TRAIL receptor 1 (TRAIL-R1), TRAIL-R2, caspase-8, and nuclear factor-kappaB (NF-kappaB).
Expression of TNFalpha, TNFRI, TRAIL, TRAIL-R1, TRAIL-R2, and NF-kappaB mRNA was detected in most samples of normal and neoplastic odontogenic tissues. Expression of caspase-8 mRNA was identified in six of 33 ameloblastomas, but not in 10 tooth germs or one malignant ameloblastoma. Immunohistochemical reactivity for TNFalpha, TRAIL, their receptors, and NF-kappaB was detected in both normal and neoplastic odontogenic tissues. Epithelial expression of TNFalpha was focal in about 50% of tooth germs and ameloblastomas, and TNFalpha expression in neoplastic cells was significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. TRAIL reactivity was evident in epithelial cells neighboring the basement membrane. Receptors for TNFalpha and TRAIL were diffusely expressed in both normal and neoplastic odontogenic epithelium. Expression of caspase-8 was found in some neoplastic cells in three of 37 ameloblastomas, but not in 10 tooth germs or five malignant ameloblastomas. Nuclear NF-kappaB expression was much lower than cytoplasmic expression in both normal and neoplastic odontogenic epithelium.
Expression of TNFalpha, TRAIL, and their receptors in tooth germs and ameloblastomas suggests that these death factors might be involved in cytodifferentiation of odontogenic epithelium and tissue structuring of ameloblastomas. Expression of caspase-8 and NF-kappaB suggests that signaling of TNFalpha and TRAIL minimally affects the biological properties of odontogenic epithelial components.
为阐明死亡受体介导的凋亡信号通路在牙源性肿瘤发生和细胞分化中的作用，对成釉细胞瘤以及牙胚中肿瘤坏死因子α（TNFα）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）及其相关分子的表达进行了分析。
采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法检测10个牙胚、40例良性成釉细胞瘤和5例恶性成釉细胞瘤组织标本中TNFα、肿瘤坏死因子受体I（TNFRI）、TRAIL、TRAIL受体1（TRAIL-R1）、TRAIL-R2、半胱天冬酶-8（caspase-8）和核因子κB（NF-κB）的表达。
在大多数正常和肿瘤性牙源性组织样本中检测到TNFα、TNFRI、TRAIL、TRAIL-R1、TRAIL-R2和NF-κB mRNA的表达。在33例成釉细胞瘤中的6例中检测到caspase-8 mRNA的表达，但在10个牙胚或1例恶性成釉细胞瘤中未检测到。在正常和肿瘤性牙源性组织中均检测到TNFα、TRAIL及其受体和NF-κB的免疫组织化学反应。TNFα的上皮表达在约50%的牙胚和成釉细胞瘤中呈局灶性，滤泡型成釉细胞瘤中肿瘤细胞的TNFα表达明显高于丛状型成釉细胞瘤。TRAIL反应在基底膜附近的上皮细胞中明显。TNFα和TRAIL的受体在正常和肿瘤性牙源性上皮中均呈弥漫性表达。在37例成釉细胞瘤中的3例的一些肿瘤细胞中发现了caspase-8的表达，但在10个牙胚或5例恶性成釉细胞瘤中未发现。在正常和肿瘤性牙源性上皮中，核NF-κB的表达远低于细胞质表达。
TNFα、TRAIL及其受体在牙胚和成釉细胞瘤中的表达表明，这些死亡因子可能参与牙源性上皮的细胞分化和成釉细胞瘤的组织结构形成。caspase-8和NF-κB的表达表明，TNFα和TRAIL的信号传导对牙源性上皮成分的生物学特性影响最小。
