The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.
We detected p63 and p53 expression using immunohistochemistry staining in 84 cases of NKTCL from Southern of China, an area with a well known high incidence of nasopharyngeal carcinoma, which is closely associated with Epstein-Barr virus infection.
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.
Collectively, these findings suggest that p53 acting as a transcription factor promotes the transcriptional activity of survivin, and further increases its protein expression and phosphorylation in the regulation of LMP1, thus, leading to G1/S cell cycle progression with no effect on apoptosis in NPC tumorigenesis.
The results showed that the radiosensitivity of CNE2sip53 was significantly lower than that of CNE2/pSUPER, indicating that p53 plays a role in mediating NPC radiosensitivity.
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.
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.
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.
Together with the radioresistance acquired by CNE2sip53 cells, our data indicate that in contrast to a previous study, p53 in this NPC cell line remains functional, which may have an important therapeutical implication.
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.
The DeltaNp63 has been postulated to have a dominant-negative effect on the function of the p53 gene and may play a role in the pathogenesis of nasopharyngeal carcinoma.
Our data suggest that these differential proteins may be associated with the function of p53 in NPC, and provide new clues to elucidate the mechanisms of inactivation and stabilization of p53 in NPC.
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).
These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.
Antisense oligodeoxynucleotides may become a promising strategy to enhance radiosensitivity in nasopharyngeal carcinoma cells with normal p53 function.
It is theorized that the cooperative expression of bcl-2 and LMP1 exists in the majority of NPC, while a minority of NPC have cooperative expression of LMP1 and mutant p53.