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Updated: Jun 21, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Dynamic telomerase gene suppression via network effects of GSK3 inhibition

Alan E Bilsland1, Stacey Hoare, Katrina Stevenson

  • 1Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Bearsden, Glasgow, United Kingdom.

Plos One
|August 4, 2009
PubMed
Abstract

Insights

Glycogen synthase kinase 3 (GSK3) inhibition suppresses human telomerase reverse transcriptase (hTERT) expression and telomere length in cancer cells. This suggests GSK3 inhibitors may be a novel cancer therapy strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Telomerase is crucial for cell immortality and a target for anti-cancer drugs.
  • Few small molecule telomerase inhibitors exist.
  • Understanding pathways regulating human telomerase reverse transcriptase (hTERT) is key for new cancer therapies.

Purpose of the Study:

  • To investigate the role of glycogen synthase kinase 3 (GSK3) in regulating hTERT expression.
  • To explore GSK3 inhibition as a potential anti-cancer strategy targeting telomerase.

Main Methods:

  • Focused promoter screen to identify regulators of hTERT reporter activity.
  • Utilized GSK3 inhibitor 6-bromoindirubin-3'-oxime in cancer cell lines and ovarian cancer xenografts.
  • Employed microarray analysis, network modeling, and oligonucleotide binding assays.
  • Performed RNAi screening of the hTERT promoter.

Main Results:

  • GSK3 inhibition suppressed hTERT expression, telomerase activity, and telomere length in cancer cells.
  • GSK3 inhibition reduced tumor growth and hTERT expression in ovarian cancer xenografts.
  • Identified extensive remodeling of transcription factors (Sp1, STAT3, c-Myc, NFkappaB, p53) at the hTERT promoter.
  • Discovered multiple kinase genes affecting hTERT promoter activity.

Conclusions:

  • GSK3 activation of hTERT contributes to cancer cell immortality and telomere homeostasis.
  • GSK3 inhibition demonstrates potential as a cancer therapeutic strategy.
  • Complex network effects of GSK3 inhibition on transcription factors warrant further investigation for therapeutic applications.

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