| Project/Area Number |
17310121
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied genomics
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
KIYAMA Ryoichi National Institute of Advanced Industrial Science and Technology, National Institute of Advanced Industrial Science and Singnaling Molecules Researth Laboratory, Principal Investigator (00240739)
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| Co-Investigator(Kenkyū-buntansha) |
SAKUMA Yasuo Nippon Medical School, Dept. Physiology, Professor (70094307)
WADA-KIYAMA Yuko Nippon Medical School, Dept. Physiology, Lecturer (60234390)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,410,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | proteome / estrogen / signal transduction / signaling cascade / neurophysiology / DNA microarray / profiling / gene function |
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| Research Abstract |
In this study, we aimed to characterize the functions and the networks of estrogen-responsive genes by means of proteomic analysis to unravel signaling pathways of the genes responding to estrogen which were revealed by expression profiling using DNA microarrays. We focused on the following subjects:
(1) Examination of hypothetical networks of estrogen-responsive genes.
We first categorized estrogen-responsive genes based on gene functions by statistical comparison of the responses to the stimulation by various chemicals, such as phenols and phthalate esters. Then, we examined signaling mechanisms by focusing on the phosphorylation of the proteins, such as MAPK and AKT2, which are specific to the non-genomic pathway and on the receptors other than the estrogen receptors. We also analyzed various cell lines for profiling the responses to various chemicals and for cross-talks with arylhydrocarbon receptors, for example. Then, we discussed the relationship between gene expression profiles obtained by focused microarray analysis and phenomes, comprehensive phenomena at the cellular or tissue levels, and what information we would get by such focused microarray analysis.
(2) Analysis on estrogen-dependent signal transducation in brain.
We analyzed alterations in gene expression at the regions in the hypothalamus, which are related to sexual differentiation, by collaboration with the researchers in Nippon Medical School. We searched signaling cascades especially for apoptosis-or cell motility-related genes(and their protein products), which were obtained by DNA microarray analysis to understand the sexual differentiation, by means of Western blotting and other techniques.
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