Investigation of developmental mechanisms of benign prostatic hyperplasia in tissue recombination model
| Project/Area Number |
18591748
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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 |
Urology
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| Research Institution | Mie University |
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Principal Investigator |
ARIMA Kiminobu Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Associate Professor (10175995)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kenichiro Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Research Assistant Professor (90397513)
SUGIMURA Yoshiki Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Professor (90179151)
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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 |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Tissue recombination / epithelial-stromal interations / fetal rat UGM / NRP152 cells / TGFa / BPH / MAPK / CK14-positive basal epithelial cells / 前立腺肥大症 / 治療効果の減退 / 画像解析 / 平滑筋と線維組織 / ゼノグラフトモデル / タムスロシン / TGFα / ラット前立腺 / 基底上皮細胞 / アンドロゲン受容体 |
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| Research Abstract |
Tissue recombination has been widely used for examining the developmental biology of the urogenital tracts such as prostate and bladder. Recombinants are generally made by mixing stromal/mesenchymal compartments with epithelial compartment, and then grafted beneath the renal capsule of immunocompromised rodent hosts. Recently, this technique has developed to make more flexible by in vitro genetic manipulation of epithelial compartments before recombining with stromal/mesenchymal compartments.
In adult prostate homeostatic epithelial-stromal interactions maintain functional differentiation and growth-quiescence. Those interactions are mediated by paracrine singals and extracellular matrix (ECM) components secreted from stroma surrounding epithelia. Recently, deregulation of epithelial-stromal interactions in normal prostate has been considered to play a critical role in the initiation and promotion of carcinogenesis. Interestingly, stromal changes are also believed to be involved in nonm
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alignant proliferative disease benign prostatic hyperplasia (BPH). In this study, we focused on the signal of an important growth factor TGFa for rat prostatic epithelial cell line NRP152.
Overexpression of TGFa in NRP152 cells did not affect cell morphology and cell proliferation. Introducing of TGFa caused significant reduction in the p42, 44 mitogen-activated protein kinase (MAP kinase) phosphorylation but not Akt in NRP152 cells. Expression of cytokeratin 14 (CK14) as basal epithelial cell marker was generally lost in parental NRP152 grafts. However, CK14-positive basal epithelial cell layer were fully lined in NRP152-TGFa grafts. Unfortunately, both recombinants of parental and NRP152-TGFa cells with rUGM did not organize into solid epithelial cords surrounded by stromal cells.
Prostatic organization including ductal branching morphogenesis, canalization, and differentiation into basal and luminal epithelial cells is mediated by a number of paracrine signals derived from mesenchymal cells. Our results suggest that TGFa may play a role in the regulation of epithelial differentiation via MAPK in prostate. Less
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to the LPB-Tag model of prostate cancer2006
Author(s)
Wang, Y., Kasper, S., Yuan, J., Jin, R.J., Zhang, J., Ishii, K., et al.
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Journal Title
Laboratory Investigation 86
Pages: 1074-1088
Related Report
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