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HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium

BACKGROUND: Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in T...

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Autores principales: Kurosu, T, Ohga, N, Hida, Y, Maishi, N, Akiyama, K, Kakuguchi, W, Kuroshima, T, Kondo, M, Akino, T, Totsuka, Y, Shindoh, M, Higashino, F, Hida, K
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048211/
https://www.ncbi.nlm.nih.gov/pubmed/21285980
http://dx.doi.org/10.1038/bjc.2011.20
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author Kurosu, T
Ohga, N
Hida, Y
Maishi, N
Akiyama, K
Kakuguchi, W
Kuroshima, T
Kondo, M
Akino, T
Totsuka, Y
Shindoh, M
Higashino, F
Hida, K
author_facet Kurosu, T
Ohga, N
Hida, Y
Maishi, N
Akiyama, K
Kakuguchi, W
Kuroshima, T
Kondo, M
Akino, T
Totsuka, Y
Shindoh, M
Higashino, F
Hida, K
author_sort Kurosu, T
collection PubMed
description BACKGROUND: Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm. METHODS: Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs. RESULTS: The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs. CONCLUSION: Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium.
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spelling pubmed-30482112012-03-01 HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium Kurosu, T Ohga, N Hida, Y Maishi, N Akiyama, K Kakuguchi, W Kuroshima, T Kondo, M Akino, T Totsuka, Y Shindoh, M Higashino, F Hida, K Br J Cancer Molecular Diagnostics BACKGROUND: Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm. METHODS: Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs. RESULTS: The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs. CONCLUSION: Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium. Nature Publishing Group 2011-03-01 2011-02-01 /pmc/articles/PMC3048211/ /pubmed/21285980 http://dx.doi.org/10.1038/bjc.2011.20 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Kurosu, T
Ohga, N
Hida, Y
Maishi, N
Akiyama, K
Kakuguchi, W
Kuroshima, T
Kondo, M
Akino, T
Totsuka, Y
Shindoh, M
Higashino, F
Hida, K
HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title_full HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title_fullStr HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title_full_unstemmed HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title_short HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium
title_sort hur keeps an angiogenic switch on by stabilising mrna of vegf and cox-2 in tumour endothelium
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048211/
https://www.ncbi.nlm.nih.gov/pubmed/21285980
http://dx.doi.org/10.1038/bjc.2011.20
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