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

从肺癌发生到转移的基因异常积累及其信号转导途径为研究肺腺癌发生过程中基因异常的积累，我们检测了小肺腺癌的遗传变异，并分析了杂合性丢失（洛）。在极早期腺癌中检测到等位基因丢失，在恶性肿瘤中染色体17 p上的LOH频率增加。肿瘤的进展。为了探讨人肺癌发生的信号转导机制，我们检测了79例肺癌组织中MAPK和STAT3的表达，MAPK磷酸化和STAT3磷酸化。MAPK在肺癌组织和正常肺组织中的表达水平无差异。磷酸化MAPK在正常肺组织中的浓度显著高于癌组织。STAT3表达有与磷酸化MAPK表达负相关的趋势。磷酸化STAT3在腺癌中的表达显著高于鳞癌。这些结果提示JAK/STAT信号转导通路在人肺腺癌的发生发展中可能比MAPK级联发挥更重要的作用。其中，我们在外显子3上发现了4个突变，它们位于稳定β-catenin的突变靶区域。我们的研究结果表明，β-catenin的激活突变，换句话说，Wnt信号转导通路激活，发生在肺癌的小子集。

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.