| Project/Area Number |
15591689
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
USUI Tsuguru Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30034060)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Kenji Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (60116564)
MATSUBARA Akio Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (10239064)
YASUMOTO Hiroaki Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (20314750)
MITA Koji Hiroshima University, Hospital, Research Associa, 病院・助手 (70304425)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Hormone independent / FGFR2IIIb / Gene therapy / Apoptosis / Radiotherapy / Chemotherapy / 腫瘍抑制 / 遺伝子移入 / 上皮・間質相互作用 / 分化誘導 |
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| Research Abstract |
The role of FGFR2IIIb in cell proliferation anddifferentiation were studied in hormone independentprostate cancer, and usefulness of combination therapyusing radiation and anticancer agent were also studied in the FGFR2IIIb transfected cell.
1)Establishment of FGFR2IIIb transfected PC-3 cell :
The growth rate of PC-3 FGFR2IIIb transfected cells was significantly slower than that of the control cells. The growth rate of the PC-3 FGFR2IIIb derived tumors was significantly slower than that of the control. PC-3 FGFR2IIIb cells were morphologically changed from PC-3 neo cells. Immunocytochemical analysis revealed a weak pancytokeratin and lactoferrin-positive staining of the control, whereas PC-3 FGFR2IIIb cells showed strong positive pancytokeratin and lactoferin immunostaining. In the apoptosis assay, most of PC-3 FGFR2IIIb cells were stained with the APOPercentage-dye.
2)Signal transduction of FGFR2IIIb :
FRS2 was identified as a tyrosine-phosphorylated protein in both PC-3 neo and PC-3 FGFR2IIIb cells stimulated with FGF-1. The signal intensity of FRS2 in PC-3 FGFR2IIIb was much stronger than that of the control. On the stimulation with FGF-7, FRS2 was strongly activated in PC-3 v cells but not in PC-3 neo cells. On stimulation with FGF-1 and FGF-7, the phosphorylation of p44/42 MAP kinase was detected in PC-3 FGFR2IIIb cells, but not in PC-3 neo cells.
3)Synergistic effects of radiation and an anticancer agent with the FGFR2IIIb
Four and 8 Gy of radiation treatment dramatically decreased the number of colonies in PC3-IIIb cells by 87.7 % and 99.6 %, respectively. The number of colonies in Mock cells bearing an empty vector was reduced by 69.4% and 95.2%, respectively. The mean cell viability on day 3 was 0.34 for PC-IIIb without docetaxel, 0.24 for PC3-IIIb1+0.01μM docetaxel, and 0.20 for PC3-IIIb + 0.1μM of docetaxel. The difference between the groups was statistically significant (p<0.0001).
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