| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Outline of Final Research Achievements |
By comparing the genomic profiles of paired non-invasive and invasive carcinoma tissues collected from patients with intraductal papillary mucinous neoplasm, we demonstrate that the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, a MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter. Re-expression of DUSP4 in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Therefore, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model. Collectively, our findings reveal a genetic mechanism by which pancreatic intraepithelial lesions progress to invasive carcinomas, and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling.
|
