2004 Fiscal Year Final Research Report Summary
FGFR2 gene mutation in human prostate cancer : Close relation to loss of hormone dependency and therapeutic application
| Project/Area Number |
15591690
|
|---|
| 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) |
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 Associate, 病院・助手 (70304425)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Fibroblast growth factor / Fibroblast growth factor receptor / Tyrosine kinase / Growth inhibition / Differentiation / Prostate cancer / Radiation / Gene therapy |
|---|
| Research Abstract |
Fibroblast growth factors (FGFs) and their receptors (FGFRs) expedite stromal-epithelial communication in development and homeostasis of the human prostate. Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors. We examined whether restoration of FGFR2IIIb by transfection in the malignant human prostate tumor PC-3 cell line restored cellular properties associated with less malignant tumors. Expression of FGFR2IIIb in PC-3 cells by transfection resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis. Furthermore, we investigated the synergistic effects of radiation with the FGFR2IIIb in PC-3 cells. Radiation dramatically decreased the number of colonies in transfected PC-3 cells. The results indicate that restoration of FGFR2IIIb to the malignant human prostate epithelial cell prototype PC-3 restores properties associated with nonmalignant tumors and normal cells. This further suggests that epithelial cell resident, homeostasis-promoting FGFR2 may be involved in suppression of malignancy and that restoration may be a candidate for gene therapy of hormone-refractory prostate cancer.
|
