Gefitinib-sensitizing mutation in esophageal carcinoma cell line Kyse450.
OBJECTIVE
The sensitivity of lung cancer to gefitinib has been found to be associated with mutations at the tyrosine kinase domain of epidermal growth factor receptor (EGFR), yet similar observations are not available in other solid tumors. We recently identified mutations in the EGFR kinase domain in primary esophageal carcinoma. The purpose of this study was to investigate if they are gefitinib-sensitizing EGFR mutations.


METHODS
We identified a missense mutation in the EGFR kinase domain, EGRFS7681, in the esophageal cancer cell line Kyse450. The sensitivity of this cell line to gefitinib was compared to an esophageal cancer cell line with wildtype EGFR, TE8, and to a lung cancer cell line, H358, known to be resistant to gefitinib. The effect of EGFR(S7681) mutation on cell growth and apoptosis was assessed.


RESULTS
As demonstrated by in vitro proliferation assay, this mutation sensitized Kyse450 cells to gefitinib. The observation of down regulation of the phosphorylated pAKT indicated gefitinib induced Kyse450 cells apoptosis via inhibition of EGFR activity


CONCLUSIONS
While more primary esophageal tumors remain to be screened for the mutations at the tyrosine kinase domain of EGFR, current observation implies that gefitinib may be worth further investigation for treatment of esophageal cancers.
Guo
Mingzhou
M
The Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Liu
Shuang
S
Herman
James G
JG
Zhuang
Hui
H
Lu
Fengmin
F
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary / Q000235:genetics; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib