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Research Paper
Differential sensitivity of A549 non small lung carcinoma cell responses to epidermal growth factor receptor pathway inhibitors
Maria L. Jaramillo, Myriam Banville, Catherine Collins, Beatrice Paul-Roc, Lucie Bourget and Maureen O'Connor-McCourt
volume 7 | issue 4
April 2008Pages: 557 - 568
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It has been demonstrated that A549 non-small cell lung cancer (NSCLC) cells are sensitive to epidermal growth factor receptor (EGFR) inhibitors in in vivo xenograft animal models, but are relatively resistant in conventional in vitro monolayer growth assays. Here, we utilized anchorage-independent cell growth/survival assays as well as motility assays and demonstrated that these tests detect the effects of two EGFR inhibitors, the small molecule inhibitor AG1478 and the ligand-blocking antibody 225 mAb, on A549 cells more sensitively than monolayer growth assays. AG1478 was more effective than 225 mAb at inhibiting EGF-stimulated anchorage-independent cell growth, in part due to its pronounced ability to inhibit cell survival, whereas 225 mAb and AG1478 were both able to inhibit cell motility. In order to determine which EGFR signalling pathway components were most strongly associated with these cell responses, we analyzed in parallel the phosphorylation levels of EGFR itself as well as several downstream pathway elements. We found that the limited ability of 225 mAb to inhibit MAPK, PI3K and STAT3 phosphorylation correlated with its inability to promote anchorage independent apoptosis, but did not correlate with its ability to inhibit motility. Based on our results in A549 cells, we propose that EGF stimulates tumour progression of NSCLC largely through effects on anchorage-independent growth and survival, as well as motility.
Authors
Maria L. Jaramillo
Myriam Banville
From the *Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2, and &Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6
Catherine Collins
From the *Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2, and &Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6
Beatrice Paul-Roc
From the *Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2, and &Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6
Lucie Bourget
Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2, and &Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6