Analysis of the function of TOB (transducer of Erb) on proliferation and differentiation of keratinocytes
| Project/Area Number |
15591182
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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 |
Dermatology
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| Research Institution | Ehime University |
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Principal Investigator |
SHIRAKATA Yuji Ehime University, School of Medicine, Instructer, 医学部, 助手 (50226320)
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| Co-Investigator(Kenkyū-buntansha) |
山崎 研志 愛媛大学, 医学部, 助手 (40294798)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | TOB / EGF / adenovirus vector / cross-induction / autocrine / knockout mouse / keratinocyte / serum free culture |
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| Research Abstract |
TOB (Transducer of Erb) has been discovered as a factor that binds to ErbB2, which is a member of EGF receptor family. TOB family consists of 6 homologous members. It has been reported that TOB is active at cell arrest stage, its expression is regulated by cell cycle, EGF receptor phosphorylation induces TOB expression, constitutive active TOB over-expression decreases cyclin D1 expression. The purpose of this study is to investigate whether TOB is involved in EGF family-related auto- and cross- induction mechanism in normal human keratinocytes. RT-PCR analysis using specific primers for each TOB family member showed that keratinocytes express TOB family mRNA. EGF stimulation upregulated TOB mRNA expression in a dose dependent manner. These results indicate that there might be a negative feedback mechanism by TOB about EGF induced proliferation in keratinocytes. To further clarify the role of TOB on EGF-induced keratinocyte growth, we constructed adenovirus vector such as Ax-TOB, AxTOB3A and AxTOB3SE. AxTOB3A is a mutant form which acts as constitutive active TOB. AxTOB3SE is a dominant -negative form of TOB. Keratinocytes were transfected with these adenovirus vectors, cell cycle and differentiation markers were analyzed at RNA level as well as protein level. Constitutive active form of TOB arrested cell cycle and induced keratinocyte differentiation. On the other hand, dominant-negative form of TOG increased S-phase cells and inhibited the expression of differentiation markers. We also established the keratinocytes from new born TOB knockout mice. We conclude that TOB is an important factor for keratinocyte-growth inhibition.
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration2005
Author(s)
Tokumaru S, Sayama K, Yamasaki K, Shirakata Y, Hanakawa Y, Yahata Y, Dai X, Tohyama M, Yang L, Yoshimura A, Hashimoto K
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Journal Title
Biochem Biophys Res Commun. 327
Pages: 100-105
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] TGF-beta is not involved in early phase growth inhibition, of keratinocytes by 1 alpha,25(OH)2vitamin D32004
Author(s)
Shirakata Y, Ueno H, Hanakawa Y, Kameda K, Yamasaki K, Tokumaru S, Yahata Y, Tohyama M, Sayama K, Hashimoto K
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Journal Title
J Dermatol Sci. 36
Pages: 41-50
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor β autoinduction : A negative feedback mechanism for keratinocyte growth2003
Author(s)
Yamasaki K, Toriu N, Hanakawa Y, Shirakata Y, Sayama K, Takayanagi A, Ohtsubo M, Gamou S, Shimizu N, Fujii M, Miyazono K, Hashimoto K
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Journal Title
J Invest Dermatol 120
Pages: 1030-1037
Description
「研究成果報告書概要(欧文)」より
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