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HTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor.

ABSTRACT: 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.

SUBMITTER: Liu N

PROVIDER: S-EPMC5062966 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor.

Liu Ning N Ding Deqiang D Hao Wanyu W Yang Fan F Wu Xiaoying X Wang Miao M Xu Xiaoling X Ju Zhenyu Z Liu Jun-Ping JP Song Zhangfa Z Shay Jerry W JW Guo Yunliang Y Cong Yu-Sheng YS

Nucleic acids research 20160620 18

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 ...[more]

PMID: 27325744

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HTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor.

Publications

hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor.

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