| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog, PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin syndrome, which is characterized by developmental defects and tumorigenicity. In order to elucidate the mechanism by which transduction of the hedgehog signal is regulated in tissues, we employed murine C3H10T1/2 cells and human fibroblasts. We investigated GLI1 transcription to assess native signal transduction, and then treated cells with a recombinant human hedgehog protein with or without serum deprivation. Hedgehog stimulation and nutritional deprivation synergistically enhanced GLI1 transcription levels, which was blocked more efficiently by vismodegib. These results indicated that the hedgehog stimulation and nutritional deprivation synergistically activated the hedgehog signaling pathway. These fibroblasts may become a significant tool for predicting the efficacies of hedgehog molecular-targeted therapies such as vismodegib.
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