The role of P38, jun-n-terminal kinase, protein kinase A and glycogen synthase kinase-3β in expression of the epidermal growth factor receptor in lung carcinoma cell lines

Objective: In most of the non-small cell lung carcinoma (NSCLC) patients, overexpression of epidermal growth factor receptor (EGFR) or activating mutations in EGFR has been playing a critical role in tumor pathogenesis. The aim of this study is to investigate the effects of P38, Jun-N-terminal kinase (JNK), Protein kinase A (PKA), and Glycogen synthase kinase-3β (GSK-3β) on EGFR expression level in an NSCLC cell line. Method: First of all, the cell line which has the highest EGFR expression level was detected among the lung carcinoma cell lines known as A549, H1299, and H1650. And then the rest of the experiments has been done in this cell line. After treatment of this cell line with specific inhibitors for P38, JNK, PKA, and GSK-3β, each group evaluated for EGFR expression level by treating with epidermal growth factor (EGF) or without EGF induction. The expression levels obtained from inhibitor groups were compared with control groups. Results: In the H1299 cell line, after treatment with specific inhibitors of P38, JNK, PKA, and GSK-3β, a statistically significant decrease in EGFR expression levels was found in groups with and without EGF induction. A higher level of EGFR expression was detected in groups treated with EGF than in those without EGF treatment. Conclusion: Our study suggests that P38, JNK, PKA, and GSK-3β may have effects on the intracellular protein level of EGFR. However, this conclusion should not be reached only by evaluating the expression level, the mechanisms affecting the intracellular EGFR level should be considered in a complex manner. In addition to EGFR-targeted therapies, identifying and targeting related signaling pathways will contribute to more effective results in cancer treatment.