Alterations of the apoptosis signaling pathways in oncogenesis of odontogenic epithelium

牙源性上皮细胞凋亡信号通路的改变

• 批准号: 16591881
• 负责人: KUMAMOTO Hiroyuki
• 金额: $ 1.15万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591881/
• 关键词: odontogenic tumor; apoptosis; signal transduction

To clarify the possible roles of the apoptosis signaling pathways in oncogenesis of odontogenic epithelium, expression of death receptor- and mitochondria-mediated pathway signaling molecules was analyzed in ameloblastomas and malignancy ameloblastomas as well as in tooth germs.1.Death receptor-mediated apoptosis signaling molecules : Representative death receptors, TNFRI and TRAIL-R1,2, and their downstream apoptosis initiator, caspase-8, were examined in tooth germs and benign and malignant ameloblastomas by RT-PCR and immunohistochemistry. Expression of TNFRI and TRAIL-R1,2 was detected in both normal and neoplastic odontogenic tissues, and they were distributed widely in epithelial components. In contrast, expression of caspase-8 was detected in a few cases of ameloblastomas, and its distribution is limited.2.Mitochondria-mediated apoptosis signaling molecule : Representative mitochondrial apoptotic pathway signaling molecules, cytochrome c, APAF-1, and caspase-9, were examined in tooth germs and benign and malignant ameloblastomas by RT-PCR and immunohistochemistry. Expression of cytochrome c, APAF-1, and caspase-9 was detected in both normal and neoplastic odontogenic tissues. Cytochrome c distribution was evident in odontogenic epithelial cells neighboring the basement membrane, whereas APAF-1 and caspase-9 were expressed in most odontogenic epithelial cells. Immunoreactivity for cytochrome c in tooth germs was slightly weaker than that in ameloblastomas and malignant ameloblastomas.3.Conclusions : The mitochondria-mediated apoptotic pathway has a role in apoptotic cell death of normal and neoplastic odontogenic epithelium, rather than the death receptor-mediated apoptotic pathway. Alterations of these apoptosis signaling molecules might be involved in oncogenesis of odontogenic epithelium.

为了阐明凋亡信号通路在牙源性上皮肿瘤发生中的可能作用，我们分析了死亡受体和线粒体介导的信号通路分子在成釉细胞瘤和恶性成釉细胞瘤以及牙胚中的表达。死亡受体介导的凋亡信号分子：采用RT-PCR和免疫组织化学方法检测牙胚和良恶性成釉细胞瘤中具有代表性的死亡受体TNFRI、TRAIL-R1、2及其下游凋亡启动物caspase-8。TNFRI和TRAIL-R1,2在正常和肿瘤牙源性组织中均有表达，它们广泛分布于上皮成分中。相反，caspase-8在少数成釉细胞瘤中表达，且分布有限。线粒体介导的凋亡信号分子：采用RT-PCR和免疫组织化学方法检测牙胚和良恶性成釉细胞瘤中具有代表性的线粒体凋亡通路信号分子细胞色素c、APAF-1、caspase-9。细胞色素c、APAF-1和caspase-9在正常和肿瘤牙源性组织中均有表达。细胞色素c在基底膜附近的成牙上皮细胞中分布明显，而APAF-1和caspase-9在大多数成牙上皮细胞中表达。细胞色素c在牙胚中的免疫反应性略弱于成釉细胞瘤和恶性成釉细胞瘤。结论：线粒体介导的凋亡通路在正常和肿瘤牙源性上皮细胞凋亡中起作用，而不是死亡受体介导的凋亡通路。这些凋亡信号分子的改变可能与牙源性上皮的肿瘤发生有关。

项目成果

K-Ras gene status and expression of Ras/MAPK signaling molecules in ameloblastomas

成釉细胞瘤中 K-Ras 基因状态和 Ras/MAPK 信号分子的表达

• 发表时间: 2004
• 期刊: Journal of Oral Pathology & Medicine 33・6
• 作者: Kumamoto H;Takahashi N;Ooya K
• 通讯作者: Ooya K

Expression of SHH signaling molecules in ameloblastomas

SHH信号分子在成釉细胞瘤中的表达

• 发表时间: 2004
• 期刊: Journal of Oral Pathology & Medicine 33・3
• 作者: Kumamoto H;Ohki K;Ooya K
• 通讯作者: Ooya K

Expression of p63 and p73 in ameloblastomas

• DOI: 10.1111/j.1600-0714.2005.00284.x
• 发表时间: 2005-04-01
• 期刊: JOURNAL OF ORAL PATHOLOGY & MEDICINE
• 影响因子: 3.3
• 作者: Kumamoto, H;Ohki, K;Ooya, K
• 通讯作者: Ooya, K

Expression of TNFα, TRAIL, and their associated molecules in ameloblastomas

成釉细胞瘤中 TNFα、TRAIL 及其相关分子的表达

• 发表时间: 2005
• 期刊: Journal of Oral Pathology & Medicine 34・5
• 作者: Kumamoto H;Ooya K
• 通讯作者: Ooya K

Expression of survivin and XIAP in ameloblastomas

成釉细胞瘤中survivin和XIAP的表达

• 发表时间: 2004
• 期刊: Virchows Archiv 444・2
• 作者: Kumamoto H;Ooya K
• 通讯作者: Ooya K