Department of Pathology, Rijeka University School of Medicine, Braće Branchetta 20, Rijeka, Croatia.
Clin Transl Oncol. 2013 Jan;15(1):65-71. doi: 10.1007/s12094-012-0889-9. Epub 2012 Jul 24.
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-κB) 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-κB in clear cell renal cell carcinoma (CCRCC).
Expression of EGFR, OPN, and p65 NF-κB 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-κB protein expression.
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-κB 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-κB protein expression (p < 0.001 and p = 0.047, respectively).
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.
表皮生长因子受体（EGFR）是一种受体酪氨酸激酶，参与与肿瘤发生相关的许多重要细胞生物学方面。EGFR 在肾癌中的作用及其 EGFR 靶向治疗的结果存在相反的证据，表明 EGFR 信号通路的复杂性。体外研究认为，骨桥蛋白（OPN）和核因子 kappa B（NF-κB）参与特定配体非依赖性 EGFR 激活，可能在 EGFR mAb 治疗耐药中发挥作用。本研究旨在分析在透明细胞肾细胞癌（CCRCC）中 EGFR 与 OPN 在蛋白和 mRNA 水平上的关系，以及它们与 NF-κB 的关系。
使用免疫组织化学分析 88 例 CCRCC 样本中 EGFR、OPN 和 p65 NF-κB 蛋白的表达，并相互比较。使用定量实时 PCR 分析 22 例 CCRCC 样本中 EGFR 和 OPN mRNA 的表达，并相互比较，同时与 NF-κB 蛋白表达进行比较。
与正常肾组织相比，CCRCC 样本中 EGFR mRNA 水平更高（p=0.012），并与 OPN mRNA 水平升高和 NF-κB 激活相关（p<0.001 和 p=0.045）。免疫组织化学染色显示出相反的关联；高 EGFR 蛋白表达与低 OPN 和 NF-κB 蛋白表达相关（p<0.001 和 p=0.047）。
CRCC 中 EGFR 基因上调，与 OPN 基因表达和 NF-kB 信号相关。OPN 和 EGFR 在蛋白水平上的反比关系可能反映了 EGFR 激活后发生的动态变化。
