| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
We extracted SATB2 and NRG1 genes as candidates for upstream regulatory genes based on a hypothesis that the aberrant expression of upstream regulatory genes caused by aberrant DNA methylation is associated with the pathogenesis of uterine leiomyomas. To infer the functions of the genes, cell lines overexpressing each gene were established and their transcriptome and pathway analyses were performed. WNT/β-catenin and TGF-β signaling related to the pathogenesis of leiomyomas were activated by both SATB2 and NRG1 overexpression. The signaling of growth factors including VEGF, PDGF and IGF1, and the retinoic acid signaling, which are associated with the growth of leiomyomas, were activated in SATB2 and NRG1 overexpression, respectively. The results indicate that SATB2 and NRG1 overexpression induced most of the signaling pathways that are currently considered to be involved in the pathogenesis of leiomyomas, suggesting that these genes have roles as the upstream regulatory factors.
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