| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Naoko 東京大学, 大学院医学系研究科, 講師 (40279352)
MUTOH Hiroyuki 自治医科大学, 医学部, 准教授 (50322392)
TSUTSUMI Ryohei 東京大学, 大学院医学系研究科, 助教 (50435872)
SAITO Yasuhiro 東京大学, 大学院医学系研究科, 助教 (30613004)
TAKAHASHI Atsushi 東京大学, 大学院医学系研究科, 助教 (00624496)
|
|---|
| Budget Amount *help |
¥233,870,000 (Direct Cost: ¥179,900,000、Indirect Cost: ¥53,970,000)
Fiscal Year 2014: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2013: ¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
Fiscal Year 2012: ¥47,970,000 (Direct Cost: ¥36,900,000、Indirect Cost: ¥11,070,000)
Fiscal Year 2011: ¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000)
Fiscal Year 2010: ¥48,880,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥11,280,000)
|
|---|
| Outline of Final Research Achievements |
Chronic infection with cagA-positive Helicobacter pylori is causally associated with gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via a bacterial microsyringe, where it acts as an oncogenic scaffold. In this work, we succeeded in solving three dimensional structure of the CagA protein. We also gained insights into the mechanism underlying CagA translocalization across the host plasma membrane. Furthermore, we identified intracellular signaling pathways perturbed by the delivered CagA protein. Using CagA-transgenic mouse model, we found that H. pylori CagA and inflammation mutually reinforce their activities and thereby create a negative spiral that instigates neoplastic transformation of epithelial cells.
|
