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Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells
Author(s) -
Ansell Anna,
Jedlinski Adam,
Johansson AnnCharlotte,
Roberg Karin
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12310
Subject(s) - cetuximab , amphiregulin , epidermal growth factor receptor , epiregulin , epidermal growth factor , cancer research , downregulation and upregulation , cell growth , cancer , biology , gefitinib , medicine , receptor , colorectal cancer , biochemistry , genetics , gene
Background Head and neck squamous cell carcinoma is frequently associated with aberrant epidermal growth factor receptor ( EGFR ) signaling, which contributes to tumor growth. Here, the functional importance of EGFR ligands in relation to proliferation and sensitivity to the EGFR ‐targeted therapy cetuximab was investigated in three tongue cancer cell lines. Methods The influence of epidermal growth factor ( EGF ), amphiregulin ( AR ), and epiregulin ( EPR ) on tumor cell proliferation and cetuximab response was evaluated by the addition of recombinant human (rh) proteins or by si RNA ‐mediated downregulation of the endogenous ligand production. The expression, activation and cellular distribution of EGFR were assessed by Western blot analysis and immunocytochemistry. Results EGF downregulation suppressed the proliferation of all investigated tumor cell lines, whereas the response to an increased level of EGF differed between EGFR ‐overexpressing and EGFR ‐non‐overexpressing cell lines. Furthermore, tumor cells consistently displayed increased cetuximab resistance upon the addition of rh EGF , whereas EGF silencing was associated with an improved cetuximab response. The data regarding AR and EPR were inconclusive. Conclusions Our data suggest that the amount of EGF is a determinant of the tumor cell proliferation rate and the response to cetuximab treatment in tongue cancer. Thus, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.