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hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor
Angiogenesis is recognized as an important hallmark of cancer. Although telomerase is thought to be involved in tumor angiogenesis, the evidence and underlying mechanism remain elusive. Here, we demonstrate that human telomerase reverse transcriptase (hTERT) activates vascular epithelial growth fact...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062966/ https://www.ncbi.nlm.nih.gov/pubmed/27325744 http://dx.doi.org/10.1093/nar/gkw549 |
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author | Liu, Ning Ding, Deqiang Hao, Wanyu Yang, Fan Wu, Xiaoying Wang, Miao Xu, Xiaoling Ju, Zhenyu Liu, Jun-Ping Song, Zhangfa Shay, Jerry W. Guo, Yunliang Cong, Yu-Sheng |
author_facet | Liu, Ning Ding, Deqiang Hao, Wanyu Yang, Fan Wu, Xiaoying Wang, Miao Xu, Xiaoling Ju, Zhenyu Liu, Jun-Ping Song, Zhangfa Shay, Jerry W. Guo, Yunliang Cong, Yu-Sheng |
author_sort | Liu, Ning |
collection | PubMed |
description | Angiogenesis is recognized as an important hallmark of cancer. Although telomerase is thought to be involved in tumor angiogenesis, the evidence and underlying mechanism remain elusive. Here, we demonstrate that human telomerase reverse transcriptase (hTERT) activates vascular epithelial growth factor (VEGF) gene expression through interactions with the VEGF promoter and the transcription factor Sp1. hTERT binds to Sp1 in vitro and in vivo and stimulates angiogenesis in a manner dependent on Sp1. Deletion of the mTert gene in the first generation of Tert null mice compromised tumor growth, with reduced VEGF expression. In addition, we show that hTERT expression levels are positively correlated with those of VEGF in human gastric tumor samples. Together, our results demonstrate that hTERT facilitates tumor angiogenesis by up-regulating VEGF expression through direct interactions with the VEGF gene and the Sp1 transcription factor. These results provide novel insights into hTERT function in tumor progression in addition to its role in telomere maintenance. |
format | Online Article Text |
id | pubmed-5062966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50629662016-10-14 hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor Liu, Ning Ding, Deqiang Hao, Wanyu Yang, Fan Wu, Xiaoying Wang, Miao Xu, Xiaoling Ju, Zhenyu Liu, Jun-Ping Song, Zhangfa Shay, Jerry W. Guo, Yunliang Cong, Yu-Sheng Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Angiogenesis is recognized as an important hallmark of cancer. Although telomerase is thought to be involved in tumor angiogenesis, the evidence and underlying mechanism remain elusive. Here, we demonstrate that human telomerase reverse transcriptase (hTERT) activates vascular epithelial growth factor (VEGF) gene expression through interactions with the VEGF promoter and the transcription factor Sp1. hTERT binds to Sp1 in vitro and in vivo and stimulates angiogenesis in a manner dependent on Sp1. Deletion of the mTert gene in the first generation of Tert null mice compromised tumor growth, with reduced VEGF expression. In addition, we show that hTERT expression levels are positively correlated with those of VEGF in human gastric tumor samples. Together, our results demonstrate that hTERT facilitates tumor angiogenesis by up-regulating VEGF expression through direct interactions with the VEGF gene and the Sp1 transcription factor. These results provide novel insights into hTERT function in tumor progression in addition to its role in telomere maintenance. Oxford University Press 2016-10-14 2016-06-20 /pmc/articles/PMC5062966/ /pubmed/27325744 http://dx.doi.org/10.1093/nar/gkw549 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Liu, Ning Ding, Deqiang Hao, Wanyu Yang, Fan Wu, Xiaoying Wang, Miao Xu, Xiaoling Ju, Zhenyu Liu, Jun-Ping Song, Zhangfa Shay, Jerry W. Guo, Yunliang Cong, Yu-Sheng hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title | hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title_full | hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title_fullStr | hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title_full_unstemmed | hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title_short | hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor |
title_sort | htert promotes tumor angiogenesis by activating vegf via interactions with the sp1 transcription factor |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062966/ https://www.ncbi.nlm.nih.gov/pubmed/27325744 http://dx.doi.org/10.1093/nar/gkw549 |
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