In:
Pathobiology, S. Karger AG, Vol. 75, No. 1 ( 2008), p. 2-8
Abstract:
〈 i 〉 Objective: 〈 /i 〉 To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of 〈 i 〉 EGFR 〈 /i 〉 on lung cancer. 〈 i 〉 Methods: 〈 /i 〉 We analyzed mutations in 〈 i 〉 EGFR 〈 /i 〉 , 〈 i 〉 KRAS 〈 /i 〉 , 〈 i 〉 TP53 〈 /i 〉 , and 〈 i 〉 ERBB2 〈 /i 〉 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines. 〈 i 〉 Results: 〈 /i 〉 Mutations in 〈 i 〉 EGFR 〈 /i 〉 were found only in adenocarcinoma (35 of 106 adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of 〈 i 〉 EGFR 〈 /i 〉 and 〈 i 〉 KRAS 〈 /i 〉 genes were observed.Mutations of 〈 i 〉 EGFR 〈 /i 〉 were well associated with a positive response to gefitinib. Cells with 〈 i 〉 EGFR 〈 /i 〉 mutations were very sensitive to gefitinib as well as siRNA-mediated knockdown of EGFR, those with 〈 i 〉 KRAS 〈 /i 〉 mutations responded poorly, and those without mutations of 〈 i 〉 KRAS 〈 /i 〉 and 〈 i 〉 EGFR 〈 /i 〉 showed moderate responses to both treatments. 〈 i 〉 Conclusions: 〈 /i 〉 Our present results imply that (1) mutation analyses of 〈 i 〉 EGFR 〈 /i 〉 and 〈 i 〉 KRAS 〈 /i 〉 provide valuable information about whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments, and (2) siRNA-mediated knockdown is effective in lung adenocarcinomas with 〈 i 〉 EGFR 〈 /i 〉 mutation, probably in those with resistance to gefitinib by acquired mutation in 〈 i 〉 EGFR 〈 /i 〉 .
Type of Medium:
Online Resource
ISSN:
1015-2008
,
1423-0291
Language:
English
Publisher:
S. Karger AG
Publication Date:
2008
detail.hit.zdb_id:
1483541-1
SSG:
12
