1997 Fiscal Year Final Research Report Summary
Cellular and Molecular Biological Study on Invasion and Metastasis of Urogenital Cancer
| Project/Area Number |
07671741
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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 | Sapporo Medical University School of Medicine |
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Principal Investigator |
MIYAO Noriomi Sapporo Medical University School of Medicine Assistant Professor, 医学部, 講師 (40200125)
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| Co-Investigator(Kenkyū-buntansha) |
YANASE Masahiro Sapporo Medical University School of Medicine Clinical Instructor, 医学部, 助手 (80291558)
TSUKAMOTO Taiji Sapporo Medical University School of Medicine Professor, 医学部, 教授 (50112454)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Prostate cancer / Invasion / Metastasis / Extracellular matrix degradation / Urokinase type-plasminogen activator / transcription factor |
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| Research Abstract |
[Background] : Although many factors influence cancer cell invasion and metastasis formation, degradation of extracellular matrices has been reported to be a crucial step. The number of patient with prostate cancer has been increasing recent years in Japan. Radical prostatectomy has been reported the best treatment for organ confined prostate cancer, clinical outcomes of locally advanced and systemic spread diseases are miserable. The mechanisms of prostate cancer cell invasion and metastasis have not been fully understood. In this project we investigated that one of the mechanisms of prostate cancer invasion and metastasis.
[Results] : In vitro invasiveness of human prostate cancer cell lines, PC-3 and LNCaP,was determined by Matrigel in vitro invasion assay system indicating that PC-3 demonstrated significant in vitro invasiveness comparing to LNCaP at 6 and 8 hours incubations (p<0.01). PC-3 demonstrated to be strongly expressed E1AF and urokinase type-plasminogen activator (u-PA) mRNA,but not in LNCaP.Deletion mutant E1AF gene was introduced to highly invasive PC-3 cells by calcium-phosphate method. u-PA zymogram revealed that PC-3 degrade u-PA and that u-PA activity on 33kD was reduced in transfectants of deletion mutant E1AF comparded to that of transfectants of empty vecor to PC-3. PC-3 transfectants of deletion mutant E1AF expressed wild type E1AF and deletion mutant E1AF by Northern blot analysis. u-PA expression was reduced in transfectants of deletion mutant E1AF but no to be reduced wild type E1AF.In vitro invasiveness of deletion mutant E1AF tranfectants was apparently suppressed in 8 hours incubation compared to that of transfectant of empty vector. CAT assay for promoter activity of u-PA gene also demonstrated the supportive results that E1AF activates trancription of u-PA gene.
[Conclusions] : Prostate cancer cell invasion was regulated by expression of u-PA and expression of u-PA is regulated by transcription factor, E1AF.
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