This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy.
Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.
Using a previously established simple and sensitive p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases.
Here, we show that caspase-3-mediated p21 cleavage involves p53 independent of triptolide (TPL)-induced S phase arrest in human type 1 nasopharyngeal carcinoma (NPC) cells.
Genomic analysis for p53 mutation and in situ hybridization for human papillomavirus showed negative results, indicating that both important molecular events in NPC or head and neck cancer play a small role in this particular type of newly developed second malignant tumor.
These results indicate that UCHL1 could deubiquitinate p53 and p14(ARF) and ubiquitinate MDM2 for p53 stabilization to promote p53 signaling, thus involved in nasopharyngeal carcinoma pathogenesis, whereas it is frequently silenced in this tumor.
Increased risk of NPC was observed among individuals carrying the variant allele and genotypes of P53 codon 72 (OR Pro vs. Arg = 1.32, 95% CI 1.18-1.47, P OR < 0.001; OR ProPro vs. ArgArg = 1.90, 95% CI 1.51-2.39, P OR < 0.001; OR ProArg + ProPro vs. ArgArg = 1.33, 95% CI 1.13-1.57, P OR = 0.001; OR ProPro vs. ArgArg + ProArg = 1.65, 95% CI 1.35-2.01, P OR < 0.001).
Western blot analysis of six samples showed a high level of expression of c-myc and cdc2 kinase and a low level of p53 protein in NPCAs that contained both HPV and EBV (n = 3).
Recent work has shown that p53 gene mutations are frequently found in Epstein-Barr virus (EBV)-positive and EBV-negative cases of Burkitt's lymphoma but not in EBV-associated undifferentiated nasopharyngeal carcinomas (NPCs).
In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53.
The positive expression of EBER-1 hybridization signals in NPC had significant associations with overexpressions of p53 (P < .001), p21ras (P = .041), and bcl-2 proteins (P < .001) and loss expression of p16 protein (P = .001).
Surprisingly, three research groups have investigated p53 mutations in NPC and found no fresh tumour specimens to contain p53 mutations in exons 4-8 of the gene.
Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies.