Oncogenic KRAS-mediated signal transduction and regulatory mechanisms for developing therapeutic strategies against lung adenocarcinoma
Project/Area Number |
26461181
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Gunma University |
Principal Investigator |
Sunaga Noriaki 群馬大学, 医学部附属病院, 助教 (70400778)
|
Research Collaborator |
MIURA YOSUKE
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | 非小細胞肺癌 / KRAS遺伝子変異 / KRAS変異 / 肺腺癌 / 分子標的治療 |
Outline of Final Research Achievements |
In KRAS-mutated lung adenocarcinoma cells, the MEK inhibitors inhibited in vitro cell growth in a dose-dependent manner, and the growth inhibitory effect was enhanced by combination with the p38 inhibitors or small interfering RNAs (siRNAs) targeting MAPK14 that encodes p38α MAPK. These results indicate that combined inhibition of MEK and p38 could effectively suppress tumor growth of KRAS-mutated lung adenocarcinoma. Meanwhile, it was found that programmed death receptor-ligand 1 (PD-L1), a ligand for the PD-1 receptor, is overexpressed in KRAS-mutated lung adenocarcinoma cell lines. In these cell lines, the PD-L1 expression was reduced either by siRNA-mediated knockdown of mutant KRAS or by inhibitors of MEK and ERK. These results indicate that oncogenic KRAS upregulates PD-L1 expression through the MEK-ERK pathway activation in lung adenocarcinoma cells. These findings provide rationales for developing therapeutic strategies against KRAS-mutated lung adenocarcinoma.
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Report
(4 results)
Research Products
(1 results)
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[Presentation] Oncogenic KRAS mutations induce PD-L1 overexpression through MAPK pathway activation in non-small cell lung cancer cells.2016
Author(s)
Yosuke Miura, Noriaki Sunaga, Kyoichi Kaira, Yusuke Tsukagoshi, Takashi Osaki, Reiko Sakurai, Takeshi Hisada, Luc Girard, John D. Minna, Masanobu Yamada.
Organizer
American Association for Cancer Research Annual Meeting 2016.
Place of Presentation
New Orleans, USA.
Related Report
Int'l Joint Research