A tumor suppressor gene p53 is mostly intact and overexpressed in NPC whereas expression of p16, a cyclin-dependent kinase inhibitory protein, is downregulated in 2/3 of NPC.
Widespread apoptosis was detected after treatment for 2-6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene.
The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2 oncoprotein, has been reported in a high percentage of cases, and also in association with EBV.
To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.
Special caution should be taken with patients with cancers such as nasopharyngeal carcinoma in which p53 mutation is infrequent and radiotherapy is the main choice of treatment.
Data also suggested that cellular miR-34b, miR-34c, miR-18a, miR‑200a/b, miR-449a, miR-31 and let-7 may be dysregulated in NPCs, and that the aberrant activation of their target genes in the p53 pathway and cell cycle enhance NPC cell survival and proliferation.
Collectively, we suggest that the p53 gene polymorphism may associate with NPC susceptibility in Thai population, particularly the Pro/Pro genotype carriers with age of >40 years.
Unlike in most human solid tumors, TP53 mutations are rare in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues, suggesting a possibility that some EBV-encoded products suppress the functions of p53.
On the whole, these findings indicate that COX-2 may play a critical role in chemotherapeutic resistance in NPC via the inhibition of chemotherapy-induced senescence via the inactivation of p53.
We concluded that there were the correlations between NPSCC subtypes with EBV infection and frequent intaking of pickled food, while aging, clinical recurrence, and TP53 gene mutations were independent predictors for the poor prognosis of nasopharyngeal carcinoma.
Multivariate analysis showed that the p53 codon 72 Pro/Pro genotype [hazard ratio (HR), 0.300; 95% confidence interval (CI), 0.092-0.983; P=0.047] and heavy smoking (≥30 pack-years) (HR, 2.899; 95% CI, 1.349-6.229; P=0.006) are independent significant prognostic factors for PFS in patients with locoregionally advanced NPC.
Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed.
These findings suggest that NOLC1 plays a role in the regulation of tumorigenesis of NPC and demonstrate that both NOLC1 and tumor protein 53 work together synergistically to activate the MDM2 promoter in NPC cells.