Project/Area Number |
22791506
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Urology
|
Research Institution | National Defense Medical College |
Principal Investigator |
KURODA Kenji 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 病院, 助教 (10306780)
|
Project Period (FY) |
2010-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 小胞体ストレス / 低酸素ストレス / GRP78 / IRE1 / 腎細胞癌 |
Research Abstract |
In renal cell carcinoma (RCC), it was reported that HIF-VEGF signaling pathway could be under the control of endoplasmic reticulum stress (ER stress). Strong expression of GRP78 was also reported to play an important role in ER stress for RCC. In 2010, we investigated the relationship between expression level of GRP78 and clinicopathological parameters using RCC specimens. Statistically significant association was found between GRP78 positivity and higher tumor grade, advanced T stage, lymphovascular invasion, regional nodal involvement, and distant metastasis. Positivity of GRP78 expression was significantly associated with shorter disease-specific and progression-free survival. Representative RCC cell lines such as Caki-1, 786O, A498, 769P showed strong expression of GRP78 and IRE1 among ER stress-related proteins. It seemed that the expression of HIF1 and HIF2 were influenced by that of IRE1. So far, inhibition of GRP78 and IRE1 could lead to more anticancer effect on RCC cells.
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