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EGFR expression is linked to osteopontin and NF-κB signaling in clear cell renal cell carcinoma

Aim and background: Epidermal growth factor receptor(EGFR) is a receptor tyrosine kinase involved in many important aspects of cell biology that are related to tumorigenesis. There are opposite evidences of the role of EGFR in renal cancer and the outcome of EGFR-targeted therapies, suggesting the complexity of EGFR signaling pathways. In vitro, osteopontin (OPN) and nuclear factor kappa B (NF-kB) are thought to be involved in specific ligand-independent EGFR activation that could have a role in resistance to EGFR mAb therapy. Aim of this study was to analyze the relationship between EGFR and OPN at the protein and mRNA level, as well as their relation to NF-kB in clear cell renal cell carcinoma (CCRCC). Materials and methods: Expression of EGFR, OPN, and p65 NF-kB protein was analyzed using immunohistochemistry and compared mutually in 88 CCRCC samples. Expression of EGFR and OPN mRNAs was analyzed using quantitative Real-time PCR in 22 CCRCC samples and compared mutually and with NF-kB protein expression. Results: Epidermal growth factor receptor mRNA level was higher in CCRCC samples in comparison with normal renal tissue (p=0.012) and was associated with high OPN mRNA level, and with NF-kB activation (p<0.001 and p=0.045, respectively). Immunohistochemical staining showed the inverse association ; high EGFR protein expression was related with low OPN and NF-kB protein expression (p<0.001 and p=0.047, respectively). Conclusion: Epidermal growth factor receptor gene is upregulated in CRCC and associated with OPN gene expression and NF-kB signaling. The inverse relation between OPN and EGFR at the protein level could probably reflect dynamic changes that EGFR undergoes following activation.

Renal cell carcinoma;  EGFR;  Nuclear factor kappa B;  Osteopontin;  Tissue array analysis

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