Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Outline of Final Research Achievements |
The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signaling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. We analyzed the effects of siROR1 treatment on the phosphorylation state using a human phospho-RTK array, which revealed a significant decrease in the phosphorylation of multiple RTKs in both NCI-H1975 and PC-9 lung adenocarcinoma cells. We found that ROR1 knockdown effectively overcame ligand-mediated EGFR-TKI resistance in PC-9 or NCI-H1975 cell. These results suggest that ROR1 repression inhibits lung adenocarcinoma cells with acquired EGFR-TKI resistance through bypass pathways. Finally, we also found that ROR1 knockdown significantly decreased the protein expression of CAV1, the essential structural component of caveolae, in lung adenocarcinoma cells.
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