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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.

Yamatodani, Takashi LU ; Ekblad, Lars LU ; Kjellén, Elisabeth LU ; Johnsson, Anders LU ; Mineta, Hiroyuki and Wennerberg, Johan LU (2009) In Journal of Cancer Research and Clinical Oncology 135. p.395-402
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cancer Research and Clinical Oncology
volume
135
pages
395 - 402
publisher
Springer
external identifiers
  • wos:000263022300009
  • pmid:18813952
  • scopus:59449100329
ISSN
1432-1335
DOI
10.1007/s00432-008-0475-2
language
English
LU publication?
yes
id
33f4a363-50c0-4eab-acc7-5604f473fb63 (old id 1242661)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18813952?dopt=Abstract
date added to LUP
2008-10-03 15:34:27
date last changed
2017-08-06 04:45:27
@article{33f4a363-50c0-4eab-acc7-5604f473fb63,
  abstract     = {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.},
  author       = {Yamatodani, Takashi and Ekblad, Lars and Kjellén, Elisabeth and Johnsson, Anders and Mineta, Hiroyuki and Wennerberg, Johan},
  issn         = {1432-1335},
  language     = {eng},
  pages        = {395--402},
  publisher    = {Springer},
  series       = {Journal of Cancer Research and Clinical Oncology},
  title        = {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.},
  url          = {http://dx.doi.org/10.1007/s00432-008-0475-2},
  volume       = {135},
  year         = {2009},
}