| Project/Area Number |
18590383
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
TAMURA Kazuhiro Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor (70281409)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Pituitary tumor / Prolactinoma / Estrogen / Somatostatin / Tissue remodeling factor / VEGF / IGFBP7 |
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| Research Abstract |
Treatment with 17B-estradiol (E2) or catechol-estrogen (4-OH E2) increased the serum levels of prolactin and the size of tumor in the animals implanted with GH3 cells. The expressions of VEGF and basic FGF as well as IGF-binding protein 7 (IGFBP7) and stathmin, a cytosolic phosphoprotein that regulates microtubule dynamics increased in the tumor tissues. E2 increased VEGF and IGFBP7 expression in cultured GH3 cells. Knocking down IGFBP7 expression stimulated tumor VEGF expression and decreased the proliferation of tumor cells. The formation of integrin B1 cluster and colonies was suppressed. Somatostatin receptor (SSTR) agonist or IGFBP7 inhibited VEGF expression, suggesting that IGFBP7 may be a target molecule that is involved in the suppression of tumor progression. Furthermore, Somatostatin inhibited the phosphorylation of ERK and induced a CDK inhibitor, p27. E2-induced MAP kinase activation via the estrogen receptor a (ERα) was suppressed by SSTR stimulation and E2 treatment down-regulates SSTR1 expression. Thus, SSTR1 is a crucial role for inhibiting the signaling pathway of proliferation under ERα.
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