Activation of PI3 kinase/AKT pathway enhances degradation of EGFR
| Project/Area Number |
21790542
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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 |
Laboratory medicine
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
KURIBAYASHI Kageaki Sapporo Medical University, 医学部, 講師 (50381257)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | EGF受容体 / PI3キナーゼ / EGF / 大腸癌 / Akt |
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| Research Abstract |
EGF receptor belongs to the receptor tyrosine kinases family that is activated by the cognate ligand including EGF, TGFα, and neuregulin. EGFR activate its downstream Ras, PI3 kinase and Akt pathway, which results in cell proliferation. Clinically, overexpression of EGFR predicts poor prognosis in many types of cancer. In this study, we analyzed the degradation mechanism of EGFR in order to enhance EGFR-targeted therapy. Akt activation and EGFR reduction took place after stimulating LS180 and SW480 colon cancer cell lines with EGF, confirmed by western blotting. LY294002, PI3 kinase inhibitor, inhibited Akt activation and subsequent EGFR degradation. Activation of PI3 kinase/Akt pathway by VEGF, or HGF did not affect the expression level of EGFR. Silencing of Akt by siRNA did not affect EGFR degradation. These results show EGFR degradation is regulated by PI3 kinase activity and tyrosine kinase activity of EGFR. Moreover, down regulation of EGFR was specific to EGF stimulation and not affected by insulin, VEGF, or HGF.
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Report
(3 results)
Research Products
(20 results)
