Accumulation of gene alteration and its signal transduction pathway from development of lung cancer to metastasis.

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Accumulation of gene alteration and its signal transduction pathway from development of lung cancer to matastasis.To study the accumulation of genetic abnormalities in the course of pulmonary adenocarcinogenesis, we examined genetic alteration in small pulmonary adenocarcinoma and analyzed loss of heterozygosity (LOH) in these tumors.Allelic losses were detected in very early adenocarcinoma and the frequently of LOHs on chromosome 17p increased during malignant progression of the tumor. Heterogenous genetic alterations were determined even in small pulmonary adenocarcinoma.In the search for the signal transduction to carcinogenesis in human lung cancer, we examined the expression of MAPK and STAT3, MAPK phosphorylation, and STAT3 phosphorylation in 79 Lung cancers. There was no difference in the MAPK expression level between cancerous tissues and normal lung tissues. The concentration of phosphoMAPK was significantly higher in normal lung tissues than in cancer tissues. STAT3 expression has a tendency to inversely correlate with phosphoMAPK expression. The increased cases of phosphos STAT3 were significantly more frequent in adenocarcinoma than in squamous cell carcinoma. These results suggest that the JAK/STAT signal transduction pathway may play a more significant role than the MAPK cascade in the carcinogenesis of human pulmonary adenocarcinoma.We searched for mutations in 166 lung cancers. Among them, we identified 4 alterations in exon3, which were in the target region of mutation for stabilizing β-catenin. Our findings suggest that activating mutations of β-catenin, in other words, Wnt signal transduction pathway activation, occurs in small subset of lung cancer.