Role of the MAPK pathway in the MGMT expression of glioma stem cells
| Project/Area Number |
23791585
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Yamagata University |
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Principal Investigator |
SATO Atsushi 山形大学, 医学部, 非常勤講師 (30455901)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | グリオーマ / 腫瘍幹細胞 / 薬剤耐性 / 化学療法 / テモゾロミド / MGMT / 脳腫瘍 / がん幹細胞 |
|---|
| Research Abstract |
The gene encoding O^6-methylguanine DNA methyltransferase MGMT, which removes the methyl group attached by temozolomide, is often silenced by promoter methylation in glioblastoma but is nevertheless expressed in a significant fraction of cases and is therefore regarded as one of the most clinically relevant mechanisms of resistance against temozolomide. This study provide lines of evidence that the MEK-ERK-MDM2-p53 pathway plays a critical role in the regulation of MGMT expression, using stem-like glioblastoma cells. This study show that, MEK inhibition reduced MDM2 expression and that inhibition of either MEK or MDM2 resulted in p53 activation accompanied by p53-dependent downregulation of MGMT expression. MEK inhibition rendered otherwise resistant stem-like glioblastoma cells sensitive to temozolomide, and combination of MEK inhibitor and temozolomide treatments effectively deprived stem-like glioblastoma cells of their tumorigenic potential. This findings suggest that targeting of the MEK-ERK-MDM2-p53 pathway in combination with temozolomide could be a novel and promising therapeutic strategy in the treatment of glioblastoma.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Targeting JNK for therapeutic depletion of stem-like glioblastoma cells2012
Author(s)
Matsuda K, Sato A, Okada M, Shibuya K, Seino S, Suzuki K, Watanabe E, Narita Y, Shibui S, Kayama T, Kitanaka C
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Journal Title
Sci Rep
Volume: 2
Issue: 1
Pages: 516-516
DOI
Related Report
Peer Reviewed
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[Journal Article] Fox03a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity2011
Author(s)
Sunayama J, Sato A, Matsuda K, Tachibana K, Watanabe E, Seino S, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, Kitanaka C
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Journal Title
Stem Cells
Volume: 29
Issue: 9
Pages: 1327-1337
DOI
Related Report
Peer Reviewed
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