Project/Area Number |
22591531
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Nippon Medical School |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
NAITO Zenya 日本医科大学, 大学院・医学研究科, 教授 (20237184)
MATSUDA Yoko 日本医科大学, 医学部, 講師 (20363187)
YAMAMOTO Tetsushi 日本医科大学, 医学部, 助教 (20453920)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | FGFR-2 IIIc / ESRP1 / siRNA / 癌幹細胞 / 選択的スプライシング / 線維芽細胞増殖 / 因子受容体 / 線維芽細胞増殖因子受容体 / FGFR2IIIc / 細胞増殖因子受容体 / FGFR2 IIIc / ESRP-1 |
Research Abstract |
Fibroblast Growth Factor Receptor 2 IIIc (FGFR-2 IIIc) was abundant in 70% of pancreatic cancer cases, which correlated with the decreased duration of the development of liver metastasis after surgery. FGFR-2 IIIc transfected cells exhibited increased proliferation in vitro and formed larger subcutaneous and orthotopic tumors. Suppression of FGFR-2 IIIc expression inhibited the proliferation of pancreatic cancer cells, whereas an anti-FGFR-2 IIIc antibody inhibited the proliferation and migration of the cells (Ishiwata et al., Am J Pathol, 2012). Epithelial Splicing Regulatory Protein1 (ESRP1) binds the FGFR2 in the intron between exon IIIb and IIIc, and primarily promotes FGFR-2 IIIb expression. ESRP1 transfected pancreatic cancer cells formed significantly fewer liver metastases as compared to control cells. Thus, high FGFR-2 IIIc levels in pancreatic cancer contribute to disease aggressiveness, and FGFR-2 IIIc may be a noveland important therapeutic target in pancreatic cancer.
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