Alterations of the apoptosis signaling pathways in oncogenesis of odontogenic epithelium

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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.