Expression of inhibitor of apoptosis family proteins in human oral squamous cell carcinogenesis.
BACKGROUND
The purpose of this study was to determine inhibitor of apoptosis (IAP) expression, its relationship with p53, and epigenetic change in oral carcinogenesis that remain to be elucidated.


METHODS
We measured IAP and p53 expression in 44 oral potentially malignant disorders and their corresponding malignant-transformed oral squamous cell carcinomas (OSCCs), and in 44 other non-transformed oral potentially malignant disorders. IAP and p53 expression in 10 fresh OSCCs, together with epigenetic change of their mutation, were also determined.


RESULTS
Normal mucosa did not express IAP/mutated p53. Oral potentially malignant disorders that underwent transformation exhibited high IAPs (>90%) and less-consistent mutated-p53 (34%) expression, whereas transformed OSCCs exhibited high IAP and mutated-p53 expression. Fresh OSCCs exhibited 80% to 100% IAP mRNA expression and 50% protein, mRNA, and p53 mutation expression. Normal tissues revealed DNA methylation of IAP, whereas cancerous tissues overexpressing IAP exhibited hypomethylation.


CONCLUSIONS
This study showed that IAP expression is an early event in oral carcinogenesis and that epigenetic and genetic pathways are associated with IAP expression in OSCC.
Department of Oral Pathology, Faculty of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yuk-Kwan
YK
Chen
Shui-Sang
SS
Huse
Li-Min
LM
Lin
D000328:Adult; D000368:Aged; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D055815:Young Adult
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C496800:NAIP protein, human; D051616:Neuronal Apoptosis-Inhibitory Protein; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases