2002 Fiscal Year Final Research Report Summary
Basic research on novel therapy for hormone-refractory prostate cancer with tyrosine kinase
| Project/Area Number |
13671654
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
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)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MUTAGUCHI Kazuaki Hiroshima University, Medical Hospital, Research Associate, 医学部附属病院, 助手 (00314758)
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)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | fibroblast growth factor / fibroblast growth factor receptor / tyrosine kinase / growth inhibition / differentiation / prostate cancer / gene therapy |
|---|
| Research Abstract |
We induced, by transfection, fibroblast growth factor receptor 2 Illb (FGFR2IIIb) kinase in hormone-independent human prostate cancer cell line, PC-3 cells. Consequently, the transfected PC-3 cells fell in a state of strong apoptosis and showed significantly reduced population growth rates in vitro and in vivo. In addition, the growth suppression was significantly accelerated by the addition of specific *igand for FGFR2IIIb, FGF-7. The expression levels of cytokeratin and lactoferrin, which are indicators for cell differentiation, markedly increased in the transfected PC-3 cells. These results indicate that the FGFR2IIIb has not only a growth suppressing but also differentiation inducing properties for hormone-independent prostate cancer cells.
In the present study, The FGFR2IIIb signaling pathway was also analyzed by Western blotting. As a result, the FRS2 signal intensity of transfected PC-3 cells was much stronger than that of control cells. After stimulation with FGF-7, FRS2 was strongly activated in transfected PC-3, but not control, cells. Also, after stimulation with FGF-1 and FGF-7, phosphorylation of p44/42 MAP kinase was detected in transfected PC-3, but not control, cells. These results indicate that the FGFR2IIIb signals in transfected PC-3 cells are closely associated with phosphorylation of FRS2 and MAP kinase. Thus the growth suppressing and differentiation inducing properties of FGFR2IIIb were considered to be induced by the activation of FRS2 and MAP kinase.
|
