|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥1,300,000 (Direct Cost : ¥1,300,000)
1. we investigated the expression of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and plasminogen activator inhibitor-1, 2 (PAI-1, PAI-2) in bladder cancer to determine the role of their gene expression in invasion and progression of bladder cancer. Expression levels of uPA, uPAR, PAI-1 and PAI-2 mRNA was significantly higher in invasive tumor, and was correlated with histological grade. We also analyzed the gene expression of SPARC in bladder cancer and its relationship with clinical-histopathological manifestation. Invasive tumors expressed significantly higher level of SPARC than superficial tumors. These results showed that uPA, uPAR, PAI-1, PAI-2, and SPARC played an important role in the tumor progression of bladder cancer.
2. The present study investigated the expression of the activated form of MMP-2 using zelatin zymography in order to define its role in urothelial cancer. Expression levels of activated forms of MMP-2 were si
gnificantly higher in invasive tumor tissue. High levels of activated forms of MMP-2 were strongly associated with shortened course-specific survival. These findings suggest that the activated form of MMP-2 plays a significant role in invasion of urothelial cancer.
3. We established non invasive and invasive urothelial cancer cell lines, and transplanted invasive urothelial cancer cell line to the bladder of SCID mice. We analyzed the mRNA localization of MT1-MMP and MMP-2 mRNA in bladder tumor tissues formed from invasive urothelial cancer cell line to the bladder of SCID mice. MT1-MMP mRNA was observed in the advanced part of tumor, and MMP-2 mRNA was observed in interstitial cells . Furthermore we are now analysing mRNAs localization in tissues obtained from surgery.
3.In situ RT-PCRによる検討
浸潤性および非浸潤性尿路上皮腫瘍の細胞株を樹立した。その細胞株をSCIDマウス膀胱に同所移植しIn situ RT-PCRによりMT1-MMPとMMP-2遺伝子発現の局在を検討したところ,MT1-MMPでは癌の先進部にMMP-2は癌細胞周囲の間質細胞に強く発現していることが示唆された。現在手術標本を用いて検討中である。 Less