![]() ![]() Since EGFR signaling is involved in several cellular mechanisms leading to tumorigenicity and resistance towards radio- and chemotherapy several inhibitory strategies such as inhibitory antibodies or small molecule inhibitors have been developed 2. The EGFR is reported to be expressed or even over-expressed in most HNSCC, assuming that this will lead to increased basal EGFR activity 1. The binding of adapter proteins can initiate diverse downstream signaling pathways such as MAPK, AKT or STAT signaling. The EGFR belongs to the family of receptor tyrosine kinases and activation by its ligands leads to trans-auto-phosphorylation at numerous tyrosine residues. The epidermal growth factor receptor (EGFR) is one of the most prominent oncogenes in head and neck squamous cell carcinoma (HNSCC). ![]() Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests. In summary, our data demonstrate that EGFR expression and activity are not well correlated. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. Overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. ![]()
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