2011 Fiscal Year Final Research Report
Functional analysis of transcription factors Egr-1 and Egr-3 in VEGF activated endothelial cells
| Project/Area Number |
22700875
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SUEHIRO Junichi 東京大学, 先端科学技術研究センター, 特任研究員 (80572601)
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| Project Period (FY) |
2010 – 2011
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| Keywords | VEGF / Egr / ChIP-sea |
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| Research Abstract |
Transcription factors, Egr-1 and Egr-3, play important roles in VEGF-activated endothelial cells. Here, I performed DNA microarray and ChIP-seq analysis in human umbilical vein endothelial cells(HUVEC) to find new targets. As a result, I found an Egr new target, Rho GTPase 1(RND1). Egr binding sites around RND1 gene located at 25kb upstream of TSS and functioned to enhance transcription. From ChIP-seq and reporter analysis, Egr and NFATc cooperatively contributed to VEGF-mediated RND1 expression. RND1 siRNA inhibited VEGF-mediated cell growth, migration, tube formation, and endothelial barrier function. In B16 melanoma solid tumor model, there were no differences between Egr-1 knockout and wildtype mice, while suppression of Egr-3 inhibited angiogenesis and tumor growth. Taken together, Egr/NFAT-mediated RND1 expression contributed to endothelial activation and there were functional differences between Egr-1 and Egr-3 in vivo.
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Research Products
(12 results)
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[Journal Article] Ets family members induce lymph angiogenesis through physical and functional interaction with Prox12011
Author(s)
Yoshimatsu Y, Yamazaki T, Mihira H, Itoh T, Suehiro J, Yuki K, Harada K, Morikawa M, Iwata C, Minami T, Morishita Y, Kodama T, Miyazono K, Watabe T
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Journal Title
Cell Sci
Volume: 124(16)
Pages: 2753-62
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[Journal Article] Epigenetically coordinated GATA2 binding is necessary for endothelium-specific endomucin expression2011
Author(s)
Kanki Y, Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro J, Wada Y, Ohta Y, Ihara S, Iwanari H, Naito M, Hamakubo T, Aburatani H, Kodama T, Minami T
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Journal Title
EMBO J
Volume: 30(13)
Pages: 2582-95
DOI
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