Gefitinib-responsive EGFR-positive colorectal cancers have different proteome profiles from non-responsive cell lines.
Biomarkers that predict response to therapy with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase remain largely uncharacterized. In order to define proteins involved in potential resistance mechanisms, we examined the effect of gefitinib (ZD1839, Iressa) in the EGFR-positive colon cancer cell lines Caco-2, DiFi, HRT-18 and HT-29. None of them exhibited an activating mutation in exons 19 or 21 of EGFR. Proteome profiling with two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry revealed 12 proteins differentially expressed in responsive and non-responsive cells. These proteins are involved in metabolic pathways, partially relevant in malignant growth and four of them are known to interact with the EGFR signalling pathway. Ubiquitin carboxyl-terminated hydrolase isozyme L1 (UCH-L1) and galectin-3 are overexpressed in the responsive cell line Caco-2, whereas fatty acid-binding protein (E-FABP) and heat shock protein (hsp) 27 are expressed more in the resistant cell lines HRT-18 and HT-29 suggesting a role in non-responsiveness of cells to gefitinib.
Loeffler-Ragg
Judith
J
Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
Skvortsov
Sergej
S
Sarg
Bettina
B
Skvortsova
Ira
I
Witsch-Baumgartner
Martina
M
Mueller
Doris
D
Lindner
Herbert
H
Zwierzina
Heinz
H
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020543:Proteome / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020543:Proteome; D011799:Quinazolines; D020893:Receptor, ErbB-3; D000077156:Gefitinib