ABSTRACT
BACKGROUND/AIMS: Mutations of the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) are important in the pathogenesis of lung cancer, and recent reports have revealed racial and geographical differences in mutation expression. METHODS: This study was conducted to investigate the prevalence of EGFR and KRAS mutations and their correlation with clinical variables in Korean patients with adenocarcinoma of the lung. Formalin-fixed adenocarcinoma specimens from 104 randomly selected patients diagnosed at Kosin University Gospel Hospital from October 1996 to January 2005 were used for the study. RESULTS: We found a high prevalence of EGFR mutations and a low prevalence of KRAS mutations. EGFR mutations were present in 24% (25 of 104) of the samples: one mutation in exon 18, 13 in exon 19, one in exon 20, and 10 in exon 21. The presence of an EGFR mutation was not associated with gender, smoking history, histological grade, age, bronchioalveolar components, or cancer stage in patients with adenocarcinoma of the lung. CONCLUSIONS: Mutations of KRAS were present in 9.6% (9 of 94) of the samples: eight in codon 12 and one in codon 13. EGFR mutations were never found in tumors with KRAS mutations, suggesting a mutually exclusive relationship.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/genetics , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Korea/epidemiology , Lung Neoplasms/genetics , Mutation , Polymerase Chain Reaction , Prognosis , Proto-Oncogene Proteins/biosynthesis , ErbB Receptors/biosynthesis , Retrospective Studies , Survival Rate , ras Proteins/biosynthesisABSTRACT
Axin is a negative regulator of the Wnt/beta-catenin pathway and is involved in the regulation of axis formation and proliferation. Involvement of Axin in the regulation of other signaling pathways is poorly understood. In this study, we investigated the involvement of Akt in growth regulation by Axin in L929 fibroblasts stimulated by EGF. Akt activity was increased by EGF treatment and Ras activation, respectively. Both the EGF- and Ras-induced Akt activations were abolished by Axin induction, as revealed by both Western blot and immunocytochemical analyses. The proliferation and Akt activation induced by EGF were decreased by Axin induction, and the effects of EGF were abolished by treatment of an Akt-specific inhibitor. Therefore, Axin inhibits EGF-induced proliferation of L929 fibroblasts by blocking Akt activation.