Epidermal growth factor receptor (EGFR) abundance correlates with p53 and Bcl-2 accumulation and patient age in a small cohort of North African nasopharyngeal carcinoma patients

Abstract

In North Africa, nasopharyngeal carcinoma (NPC) is characterized by a bimodal distribution involving a juvenile (≤ 30 years old) and an elder population (>30 years old). The Epstein Barr virus oncogene LMP1, the anti-apoptotic Bcl-2 protein and the tumor suppressor p53 have recently emerged as biomarkers of the disease. EGFR/ErbB1 expression is detected in the majority of NPC tumors with advanced disease. To obtain greater insight into the potential oncogenic mechanisms specific to these two NPC populations, we examined the correlation between EGFR expression and patient age, and determined the molecular profiles of its associations with the biomarkers of NPC. We performed an immunohistochemical analysis of the latter molecules in NPC specimens from eleven Algerian patients (six patients ≤ 30 years of age and five patients >30 years of age) using the LSAB method. Evaluation of the biopsies, based on the intensity of staining and the percentage of positive cells, showed that LMP1 expression was higher in patients under 30 years of age. Conversely, EGFR, like Bcl-2 and p53, was significantly up-regulated in tumors from elderly patients. Analysis of all tumors showed that EGFR expression was constantly (100%) associated with high p53 nuclear accumulation and Bcl-2 expression in LMP1-positive tissues. Biopsies negative for Bcl-2 staining were found to display low amounts of p53 (100%), and to be constantly negative for EGFR (100%). Molecular classification of all NPC tissues showed that the majority of patients displaying a EGFR+/LMP1+/Bcl-2+/p53-high molecular pattern were in the older age group. On the other hand, the most of the EGFR negative results were associated with the juvenile form of the disease and were characterized by an important diversity of molecular patterns. Our preliminary results suggest that in Algerian patients, the bimodal distribution of NPC might be related to distinct expression profiles of viral and cellular biomarkers of NPC.

Oxymatrine induces nasopharyngeal cancer cell death through inhibition of PI3K/AKT and NF-κB pathways

“…p53 has been reported to have at close relationship with human tumors, and functions to block cell cycle, inhibit cell proliferation, induce cell differentiation, initiate apoptosis and maintain the stability of genome (16). In the present study, higher concentrations of oxymatrine treatment (6 and 8 mg/ml) significantly induced the protein expression of p53 in NPC HK-1 cells.…”

“…Bcl2 is an apoptosis-regulator that has been thoroughly studied, and its change in expression not only affects normal apoptosis of damaged DNA cells and abnormal cells, but also the apoptosis of tumor cells (16). Bcl2 proteins are highly expressed in NPC tissues and atypical hyperplasia epithelium, which suggested that Bcl2 proteins may serve an important role in the early stage of NPC, and the overexpression of Bcl2 may also be related to the inhibition of the apoptosis of NPC (17).…”

Toxicogenomic evaluation of liver responses induced by acrylamide and glycidamide in male mouse liver

“…EGFR (epidermal growth factor receptor) is involved in many pathways related to cancer in vivo The most common way is that it could activate the Ras protein by dimerization and lead to the phosphorylation cascade and then stimulate the PI3K/Akt signaling pathway (Ono and Kuwano 2006). It has been proved that the expressions and functions of EGFR have abnormities in several kinds of human tumor issues and tumor cell lines (Bourouba 2011;Hwangbo 2013). Data presented in Shan et al (2014) demonstrated that low dose of AA was able to increase the proliferation of HepG2 cells through up-regulating EGFR expression.…”

MicroRNA-141 suppresses growth and metastatic potential of head and neck squamous cell carcinoma

“…Western blotting and real-time PCR showed that this may reflect an inhibitory effect of miR-141 on expression of bcl-2 (Fig. 4C-F), a downstream EGFR effector [9].…”