Gefitinib-sensitizing mutation in esophageal carcinoma cell line Kyse450.

Abstract:

PURPOSE: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. EXPERIMENTAL DESIGN: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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Guo M,Liu S,Herman JG,Zhuang H,Lu F

doi

10.4161/cbt.5.2.2318

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

152-5

issue

2

eissn

1538-4047

issn

1555-8576

pii

2318

journal_volume

5

pub_type

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