MDM2 overexpression with alteration of the p53 protein and gene status in oral carcinogenesis.
In this study, to better understand the mechanism of oral squamous cell carcinoma (SCC) carcinogenesis, alterations of the p53 gene and overexpression of MDM2 and p53 were analyzed in 38 oral SCC samples. Twelve of the 38 specimens revealed mutant-type p53. Moreover, coexpression of MDM2 and p53 was found most frequently in dysplastic lesions (P < 0.05). Expression of MDM2 and p53 was significantly increased in accordance with the histological progression of multistep carcinogenesis (P < 0.05). No significant correlation was found between the expression of MDM2 and the alteration of p53 protein or p53 gene status. MDM2 overexpression with mutant p53 was significantly associated with poorly differentiated SCCs (P < 0.05) and tumor stages III and IV of oral SCCs (P < 0.05). These results suggest that MDM2 overexpression is an early event in oral carcinogenesis through the functional inactivation of the wild-type p53, and corresponding alterations of MDM2 and p53 contribute to the oral carcinogenesis. We propose that it would be clinically more instructive to evaluate MDM2 overexpression combined with p53 gene status, compared to the evaluation of either MDM2 or p53 alteration alone.
Li
X J
XJ
Department of Dentistry and Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan.
Murai
M
M
Koyama
T
T
Wang
D Y
DY
Hashimoto
K
K
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2