| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Outline of Final Research Achievements |
We established GEM-resistant cells (MIA-GEMR) from MIA PaCa-2 cells and analyzed signaling pathway associated with the KRAS mutation MIA-GEMR cells showed the epithelial-mesenchymal transition phenotype and invasiveness, which were similarly induced by the KRAS mutation in colorectal cancer cells. The genes differentially expressed between MIA-GEMR and MIA PaCa-2 cells were compared with those observed between the human colorectal cancer HCT116 cells and HKe3 cells. Notably, the common genes associated with mutant KRAS regulation overlapped with stem cell-specific genes and TGF-β1 target genes, suggesting the crucial role of mutant KRAS in determining the morphology and microenvironment. Furthermore, the phosphodiesterase inhibitor resveratrol suppressed the growth of MIA-GEMR. These results suggest that TGF-β1 signaling downstream of oncogenic KRAS is involved in the onset of GEM resistance in MIA PaCa-2 cells.
|
