Epidermal growth factor receptor status and persistent activation of Akt and p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and colon cancer cell lines.

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Yamatodani, TakashiLund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

Epidermal growth factor receptor status and persistent activation of Akt and p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and colon cancer cell lines.

Article/chapterEnglish2009

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2008-09-24
Springer Science and Business Media LLC,2009

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LIBRIS-ID:oai:lup.lub.lu.se:33f4a363-50c0-4eab-acc7-5604f473fb63
https://lup.lub.lu.se/record/1242661URI
https://doi.org/10.1007/s00432-008-0475-2DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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OBJECTIVE: The aim of this study was to investigate the effect of epidermal growth factor receptor (EGFR) blockade on cell survival and on downstream signalling pathways using the monoclonal antibody cetuximab. METHODS: We used three colon cancer cell lines, of which one was EGFR-negative, and two head and neck squamous cell carcinoma (HNSCC) lines. EGFR expression and gene copy number were measured by immunohistochemistry and FISH analysis, respectively. The effect of cetuximab, irradiation or the combination of both on cell growth was estimated by SRB assay. Western blotting was used to determine the phosphorylation of intracellular signalling proteins and cell cycle phase distribution was measured by flow cytometry. RESULTS: The addition of cetuximab had only limited effects on cell growth, with a maximum inhibition of approximately 30%, but was correlated with the amount of protein expression and gene copy number of EGFR. When combined with irradiation, the effect of cetuximab was only additive and not dependent on the inherent radio-sensitivity of the cell lines. Persistent phosphorylation of Akt and/or p44/42 MAPK was detected by western blot in all of the cell lines, whereas there was no phosphorylation of Jak2 or STAT3. CONCLUSIONS: None of these factors alone could predict the sensitivity to cetuximab. Rather, the results suggest that it might be necessary to determine the activation status of several intracellular signalling proteins to better predict the sensitivity to cetuximab treatment.

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Ekblad, LarsLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-lel (author)
Kjellén, ElisabethLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-ekj (author)
Johnsson, AndersLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-ajo (author)
Mineta, Hiroyuki (author)
Wennerberg, JohanLund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onh-jwe (author)
Öron-, näs- och halssjukdomar, LundSektion IV (creator_code:org_t)

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In:Journal of Cancer Research and Clinical Oncology: Springer Science and Business Media LLC135, s. 395-4021432-13350171-5216

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