| Project/Area Number |
20790490
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Gifu University |
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Principal Investigator |
SEIJI Adachi Gifu University, 大学院・医学系研究科, 助教 (50467205)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | EGCG / EGFR / p38MAPキナーゼ / 脂質ラフト / 内在化 / 受容体チロシンキナーセ / p38MAPK / セリンリン酸化 / 受容体チロシンキナーゼ / p38 MAPK / internalization / recycle |
|---|
| Research Abstract |
We previously reported that (-)-epigallocatechin gallate (EGCG) in green tea alters plasma membrane organization and causes internalization of epidermal growth factor receptor (EGFR), resulting in the suppression of colon cancer cell growth. In the present study, we investigated the detailed mechanism underlying EGCG-induced downregulation of EGFR in SW480 colon cancer cells. Prolonged exposure to EGCG caused EGFR degradation, concurrently inducing phosphorylation of p38 mitogen-activated protein kinase (MAPK). The inhibition of p38 MAPK by SB203580, a specific p38 MAPK inhibitor, or p38 MAPK-siRNA suppressed the internalization and subsequent degradation of EGFR induced by EGCG. Moreover, EGCG caused phosphorylation of EGFR at Ser1046/1047, a site which is critical for its downregulation and this was also suppressed by SB203580 or siRNA of p38 MAPK. Taken together, our results strongly suggest that phosphorylation of EGFR at serine 1046/1047 via activation of p38 MAPK plays a pivotal role in EGCG-induced downregulation of EGFR in colon cancer cells.
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