Detection of mitochondria-mediated apoptosis signaling molecules in ameloblastomas.
BACKGROUND
To investigate the roles of the apoptosis signaling pathway mediated by mitochondria in oncogenesis and cytodifferentiation of odontogenic tumors, expression of pathway signaling molecules was analyzed in ameloblastomas as well as in tooth germs.


METHODS
Tissue specimens of 12 tooth germs, 41 benign ameloblastomas, and five malignant ameloblastomas were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry to determine the expression of cytochrome c, apoptotic protease-activating factor-1 (APAF-1), caspase-9, and apoptosis-inducing factor (AIF).


RESULTS
The mRNA expression of APAF-1, caspase-9, and AIF was detected in all samples of normal and neoplastic odontogenic tissues. Immunohistochemical reactivity for cytochrome c, APAF-1, caspase-9, and AIF was detected in both normal and neoplastic odontogenic tissues. Expression of cytochrome c and AIF was evident in odontogenic epithelial cells neighboring the basement membrane, and APAF-1 and caspase-9 were detected in most odontogenic epithelial cells. Immunoreactivity for cytochrome c in tooth germs was slightly weaker than that in benign and malignant ameloblastomas. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed a decrease or loss of immunoreactivity for these mitochondria-mediated apoptosis signaling molecules. Expression of AIF was obviously low in ameloblastic carcinomas.


CONCLUSIONS
Expression of cytochrome c, APAF-1, caspase-9, and AIF in tooth germs and ameloblastomas suggests that the mitochondria-mediated apoptotic pathway has a role in apoptotic cell death of normal and neoplastic odontogenic epithelium. Expression of these mitochondrial apoptosis signaling molecules might be involved in oncogenesis, cytodifferentiation, and malignant transformation of odontogenic epithelium.
Kumamoto
Hiroyuki
H
Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan. kumamoto@mail.tains.tohoku.ac.jp
Ooya
Kiyoshi
K
D000564:Ameloblastoma / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D053477:Apoptotic Protease-Activating Factor 1; D001485:Basement Membrane / Q000473:pathology; D053453:Caspase 9; D020169:Caspases / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D045304:Cytochromes c / Q000032:analysis; D004847:Epithelial Cells / Q000473:pathology; D005420:Flavoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis; D008928:Mitochondria / Q000502:physiology*; D011506:Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014083:Tooth Germ / Q000166:cytology
C494829:AIFM1 protein, human; C506592:APAF1 protein, human; D051033:Apoptosis Inducing Factor; D053477:Apoptotic Protease-Activating Factor 1; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D045304:Cytochromes c; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases