| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
In this research project, I analyzed the molecular mechanism underlying the acquisition of gefitinib, the EGFR specific tyrosine-kinase inhibitor, resistance in EGFR-positive non-small-cell lung cancer (NSCLC), and found that the expression of hypoxia-inducible factor (HIF)-1 is involved in gefitinib-resistance. In gefitinib-sensitive NSCLC cells, the expression of HIF-1alfa was suppressed by gefitinib treatment. In contrast, this suppression was not observed under HGF, which is known to induce gefitinib-resistance, stimulation and in gefitinib-resistant cells by mutation of tumor suppressor PREN. In addition, HIF-1 high expressing cells, the expression of anti-apoptotic Bcl-2 family proteins was enhanced. Moreover, I found that Erk signal-dependent stabilization of HIF-1alfa is involved in lung cancer stem cell maintenance. From these results, I showed that HIF-1 is important for acquisition of gefitinib-resistance and cancer stem cell maintenance in NSCLC cells.
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