K-ras gene mutation enhances motility of immortalized airway cells and lung adenocarcinoma cells via Akt activation: possible contribution to non-invasive expansion of lung adenocarcinoma.

摘要: Point mutations of the K-ras gene, which are found in 10 to 30% lung adenocarcinomas, regarded as being an early event during carcinogenesis. Autonomous vigorous motility neoplastic cells, well growth and survival advantages, considered be necessary for cancer development progression. The present study describes contributions gene mutation its downstream pathway via phosphatidylinositol 3-OH kinase (PI3K)-Akt cell immortalized human peripheral airway epithelial (HPL1D) adenocarcinoma cells (A549, H820, TKB6, TKB14). We have also evaluated relationship between pathological events K-ras-Akt using surgically resected tumors. HPL1D transfected with mutated (HPL-V12) showed a significant increase compared those empty vector (HPL-E) or wild-type (HPL-K). enhanced HPL-V12 was markedly reduced by either treatment inhibitors ras, PI3K, and/or MEK, transfection dominant-negative mutant Akt (dnAkt). bearing (A549 H820) consistently higher levels motilities than without (TKB6 TKB14), A549 H820 were significantly inhibited dnAkt transfection. These results suggest that could enhance through involving PI3K-Akt. Actually, among tumors, adenocarcinomas tended show frequency intensity immunoreactivity phosphorylated (p-ser473Akt) mutation, supporting vitro observation can activate PI3K-Akt pathway. Immunoreactivity p-ser473Akt seen pre-malignant lesions at similar advanced adenocarcinomas,. No correlation lymphatic/organ metastasis prognosis. taken together might facilitate period carcinogenesis may contribute their non-invasive expansion along alveolar septa, rather invasion metastasis.