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

First Author  Liu N Year  2016
Journal  Nucleic Acids Res Volume  44
Issue  18 Pages  8693-8703
PubMed ID  27325744 Mgi Jnum  J:250264
Mgi Id  MGI:5923255 Doi  10.1093/nar/gkw549
Citation  Liu N, et al. (2016) hTERT promotes tumor angiogenesis by activating VEGF via interactions with the Sp1 transcription factor. Nucleic Acids Res 44(18):8693-8703
abstractText  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.
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