| Project/Area Number |
17591675
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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 | Shiga University of Medical Science |
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Principal Investigator |
ISONO Takahiro University of Medical Science, Central Research Laboratory, Associate Professor, 医学部, 助教授 (20176259)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Hirokazu Shiga University of Medical Science, Central Research Laboratory, Associate Professor, 医学部, 助教授 (30176440)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | bladder cancer / cancer cells / metastasis / invasiveness / periostin / transcript variants / TAK1 |
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| Research Abstract |
In this study, we investigated whether the alternative splicing events actually occur in the bladder cancer tissues and we revealed the role of the spliced variants of periostin for the invasiveness and metastasis of cancer cells.
1.We examined the expression of wild-type (WT) and spliced variants of periostin mRNA in normal bladder and bladder cancer tissues. Although both WT and spliced periostin mRNA were expressed in all cases of normal bladder, no WT periostin mRNA was detected in transitional cell carcinomas (TCC) of bladder. Spliced variants of periostin were detected in 45% of TCC tissues.
2.The strong belt-like expression of periostin protein was obserbed in the stroma just beneath the normal bladder epithelium by immunohistochemical examination, whereas it was mostly attenuated in bladder cancer tissues, suggesting a role of periostin for protecting the tumor expansion.
3.In the ectopic expression by retrovirus vector, WT periostin could suppress in vitro invasiveness and in vivo lung metastasis of cancer in nude mice. But spliced variant, which is predominantly expressed in bladder cancer tissues, did not. show the suppressor activity on in vitro invasiveness and in vivo metastasis of cancer cells. These results indicate that the loss of WT periostin by down-regulation and/or alternative splicing, which produces Variant I, is closely correlated with the progression of bladder cancer.
4.We isolated TAB1 for the binding protein with WT periostin from ectopic overexpression system by proteomics analysis. Then we found that periostin is able to activate TAK1, which was a binding partner of TAB1, in co-transfection experiments of 293T cells. These findings suggest that TAK1 play a role in the suppression of invasion by periostin and bladder carcinogenesis.
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