Confirmatory assay for modulation of the human telomerase reverse transcriptase promoter in HCT116 cells

Keith, N. and Bilsland, A. (2017) Confirmatory assay for modulation of the human telomerase reverse transcriptase promoter in HCT116 cells. [Data Collection]

Collection description

Immortalisation is a hallmark of cancer commonly achieved by transcriptional reactivation of the telomerase reverse transcriptase gene TERT, leading to inappropriate telomere maintenance. Multiple transcription factors modulate the TERT promoter, orchestrated by the activities of a range of upstream signalling pathways. Previous studies have identified many of the pathways which individually contribute to activate or repress telomerase levels in cancer cells, resulting in a highly complex picture of TERT regulation. The pathways of TERT activation or suppression could be appropriate therapeutic targets in cancer or in telomeropathies such as dyskeratosis which are associated with loss of telomere stability.

To identify small molecule regulators of TERT transcriptional regulation, activity of the TERT core gene promoter region was monitored using firefly luciferase. Reporter pGL3-TERT contains the TERT promoter region -585/-9, relative to the translational start site, cloned in the Promega vector PGL3-basic. Telomerase positive A2780 ovarian carcinoma cells are transiently transfected with the reporter construct and subsequently treated with small molecules to detect up- or down-regulation of luciferase activity. Derivatives of compound C430-0073, identified in screen TELO-01 were tested in dose responses in the HCT116 cell line.

Funding:
College / School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Date Deposited: 15 Aug 2019 13:34
URI: https://researchdata.gla.ac.uk/id/eprint/865

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Keith, N. and Bilsland, A. (2017); Confirmatory assay for modulation of the human telomerase reverse transcriptase promoter in HCT116 cells

PubChem

https://researchdata.gla.ac.uk/865

Retrieved: 2024-03-19