2002 Fiscal Year Final Research Report Summary
Study on molecular mechanism of the development in hormone independence of human prostate carcinoma and application for new therapy.
| Project/Area Number |
13470333
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 Tsugurun 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) |
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)
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)
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)
MUTAGUCHI Kazuaki Hiroshima University, Medical Hospital, Research Associate, 医学部附属病院, 助手 (00314758)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Hormone independent / FGFR2IIIb gene / Androgen Receptor / FRS2 phosphorilation / Gene therapy / Signal pathway / Apolosis |
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| Research Abstract |
The role of FGFR2IIIb in cell proliferation and differentiation were studied in hormone independent human prostate cancer, and usefulness of FGFR2IIIb gene therapy were also studied.
1) Establishment of FGFR2IIIb transected PC-3 cell : The growth rate of PC-3 R2IIIb transfectant cells was significantly slower than that of the control cells. FGF-7 significantly inhibited the proliferation of PC-3 R2IIIb cells. The growth rate of the PC-3 R2IIIb-derived tumors was significantly slower than that of the control. PC-3 R2IIIb cells were morphologically changed from PC-3 neo cells. Immunocytochemical analysis revealed a weak pancyt okeratin and lactoferrin-positive staining of the control, whereas PC-3 R2IIIb cells showedstrong positive pancytokeratin snd lactoferin immunostaining. In the apoptosis assay, most of PC-3 R2IIIb cells weie stained with the APO Percentage-dye.
2) Cross-talk between androgen receptor and FGFR2IIIb : Luciferase activity were determined in Androgen Receptor gene transfeted PC-3 cell on the presence of FGF-7 and DHT. Increased level of activity was observed in the cell on the presence of FGF-7. So, Cross-talk system between androgen receptor and FGFR2IIIb was suspected.
3) Signal transduction of FGFR2IIIb : FRS2 was identified as atyrosine-phosphorylated protein in both PC-3 neo and PC-3 R2IIIb cells stimulated with FGF-1. The signal intensity of FRS2 in PC-3 R2IIIb was much stronger than that of the control. On stimulation with FGF-7, FRS2 was strongly activated in PC-3 R2IIIb 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 R2IIIb cells, but not in PC-3 neo cells.
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