Adenomatous polyposis coli gene mutation and decreased wild-type p53 protein expression in oral submucous fibrosis: a preliminary investigation.
OBJECTIVE
The purpose of this study was to identify the adenomatous polyposis coli (APC) tumor suppressor gene mutation and level of wild-type p53 protein expression in patients with oral submucous fibrosis (OSF).


METHODS
Cells from OSF and control subjects were cultured in Dulbecco modified Eagle medium with 10% fetal bovine serum at 37 degrees C. Genomic DNA was extracted from cultured cells and used as a template for polymerase chain reaction amplification of the APC tumor suppressor gene. The presence of wild-type p53 protein in cell lysates of cultured cells was analyzed by Western blot. Data were analyzed by the sign test for nonparametric samples and by analysis of variance.


RESULTS
The results showed that the APC gene of explant cultured cells from OSF patients (8/8) had a CGA-to-GGA transition mutation at codon 498 that resulted in an Arg-to-Gly missense mutation (P <.01). All (8/8) normal HGF cultures revealed expression of the wild-type APC protein. Cells cultured from 7 of 8 OSF patients were also found to have a single nucleotide deletion at nucleotide 1494 that resulted in creating a stop codon (TGA) at codon 504 (P <.01). This created a premature signal for the endpoint of translation and thus resulted in the generation of a truncated protein product that encodes a polypeptide of 503 amino acid residue. It was found that wild- type p53 protein in human gingival fibroblast cell cultures was significantly higher than in OSF cells (P <.01).


CONCLUSIONS
Alterations of the APC and wild-type p53 tumor suppressor genes in OSF may imply a risk for progression to oral cancer.
Liao
P H
PH
Departmnent of Dentistry, Chung Shan Medical and Dental College, Taichung, Taiwan, ROC.
Lee
T L
TL
Yang
L C
LC
Yang
S H
SH
Chen
S L
SL
Chou
M Y
MY
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000704:Analysis of Variance; D001120:Arginine / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D003062:Codon / Q000235:genetics; D003596:Cytosine; D004273:DNA, Neoplasm / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017491:Genes, APC / Q000235:genetics*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism; D005998:Glycine / Q000235:genetics; D006147:Guanine; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009914:Oral Submucous Fibrosis / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D006147:Guanine; D003596:Cytosine; D001120:Arginine; D005998:Glycine