{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T04:39:30Z","timestamp":1726029570975},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T00:00:00Z","timestamp":1423526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007435","name":"\u00c5ke Wiberg Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007435","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Head and neck squamous cell carcinoma is frequently associated with aberrant epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) signaling, which contributes to tumor growth. Here, the functional importance of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> ligands in relation to proliferation and sensitivity to the <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\u2010targeted therapy cetuximab was investigated in three tongue cancer cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The influence of epidermal growth factor (<jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content>), amphiregulin (<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>), and epiregulin (<jats:styled-content style=\"fixed-case\">EPR<\/jats:styled-content>) on tumor cell proliferation and cetuximab response was evaluated by the addition of recombinant human (rh) proteins or by si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated downregulation of the endogenous ligand production. The expression, activation and cellular distribution of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> were assessed by Western blot analysis and immunocytochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content> downregulation suppressed the proliferation of all investigated tumor cell lines, whereas the response to an increased level of <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content> differed between <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\u2010overexpressing and <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\u2010non\u2010overexpressing cell lines. Furthermore, tumor cells consistently displayed increased cetuximab resistance upon the addition of rh<jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content>, whereas <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content> silencing was associated with an improved cetuximab response. The data regarding <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EPR<\/jats:styled-content> were inconclusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data suggest that the amount of <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content> is a determinant of the tumor cell proliferation rate and the response to cetuximab treatment in tongue cancer. Thus, <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content> is a potential predictive biomarker of poor cetuximab response and a possible treatment target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12310","type":"journal-article","created":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T18:26:53Z","timestamp":1423765613000},"page":"9-16","source":"Crossref","is-referenced-by-count":14,"title":["Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells"],"prefix":"10.1111","volume":"45","author":[{"given":"Anna","family":"Ansell","sequence":"first","affiliation":[{"name":"Division of Oto\u2010Rhino\u2010Laryngology and Head and Neck Surgery Department of Clinical and Experimental Medicine Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Jedlinski","sequence":"additional","affiliation":[{"name":"Division of 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