ArticleJournal of cancer research and clinical oncology2005
The tamoxifen-induced suppression of telomerase activity in the human hepatoblastoma cell line HepG2: a result of post-translational regulation.
Article in Journal of cancer research and clinical oncology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Hepatoblastoma: an investigation of diagnostic, prognostic, and therapeutic gene targets and biomarkers.Pediatric research · 2026Pooled it
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- Human telomerase activity regulation.Molecular biology reports · 2011Review
- Application of the McMurry coupling reaction in the synthesis of tri- and tetra-arylethylene analogues as potential cancer chemotherapeutic agents.Bioorganic & medicinal chemistry · 2009Article
- Role of sex steroid receptors in pathobiology of hepatocellular carcinoma.World journal of gastroenterology · 2008Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePatients with advanced hepatocellular carcinoma (HCC) have shown to benefit from tamoxifen treatment. The mechanisms of tamoxifen action in HCC, however, are not yet clearly understood. Results from studies on the human hepatoblastoma cell line HepG2 provide evidence that estrogen-receptor-alpha-independent antiproliferative actions of tamoxifen in HCC are mediated by the suppression of telomerase activity [5]. MATERIALS AND
methodsWe investigate the pathway of the tamoxifen-induced down-regulation of telomerase activity, using HepG2 cells incubated over 24 h or 48 h in the presence of 20 microM tamoxifen.
resultsThe transcriptional levels of the three telomerase core components-human telomerase RNA (hTR), human telomerase reverse transcriptase (hTERT) (all variants), and telomerase-associated protein (TP1)-did not change during tamoxifen treatment, as revealed by RT-PCR analysis. Furthermore, the hTERT splice pattern was not shifted from the active full-length variant (+alpha/+beta) to the inactive deletion variants (-alpha; -beta; -alpha/-beta) and the level of the 120 kDa hTERT full-length protein remained constant, as shown by Western blot analysis. Protein kinase C (PKC) activity has been suggested to be crucial for post-translational up-regulation of telomerase activity. In HepG2 cells, we observed a tamoxifen-induced suppression of the total protein kinase C (PKC) activity (cytosolic and membrane-bound). Inhibition of PKC with bisindolylmaleimide I resulted in a reduction of telomerase activity, as revealed by TRAP-assay. Alpha-tocopherol (vitamin E) diminished the effects of tamoxifen on PKC-activity as well as on telomerase activity.
conclusionsWe conclude that the tamoxifen-induced decrease of telomerase activity in HepG2 cells is mediated post-translationally via suppression of PKC-activity.
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