ArticleBritish journal of cancer2007
Expression of thymidylate synthase in human cells is an early G(1) event regulated by CDK4 and p16INK4A but not E2F.
Article in British journal of cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- MRF: a tool to overcome the barrier of inconsistent genome annotations and perform comparative genomics studies for the largest animal DNA virus.Virology journal · 2023Article
- Indisulam targets RNA splicing and metabolism to serve as a therapeutic strategy for high-risk neuroblastoma.Nature communications · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Proteomics of Sentinel Lymph Nodes in Early Breast Cancer for Identification of Thymidylate Synthase as a Potential Biomarker to Flag Metastasis: A Preliminary Study.Cancer management and research · 2020Article
- The Role of Mitochondria in Drug-Induced Kidney Injury.Frontiers in physiology · 2020Review
- Cell cycle regulation of folate-mediated one-carbon metabolism.Wiley interdisciplinary reviews. Systems biology and medicine · 2018Review
- Thymidylate synthase predicts poor response to pemetrexed chemotherapy in patients with advanced breast cancer.Oncology letters · 2018Article
- Distinctive features and differential regulation of the DRTS genes of Arabidopsis thaliana.PloS one · 2017Article
- Use of Fluorescence Lifetime Imaging Microscopy (FLIM) as a Timer of Cell Cycle S Phase.PloS one · 2016Article
- DEC1 regulates breast cancer cell proliferation by stabilizing cyclin E protein and delays the progression of cell cycle S phase.Cell death & disease · 2015Article
- The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress.Nucleic acids research · 2014Article
- Article
- Dose- and time-dependent expression patterns of zebrafish orthologs of selected E2F target genes in response to serum starvation/replenishment.Molecular biology reports · 2011Article
- Thymidylate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cells.Journal of cancer research and clinical oncology · 2011Article
- Effect of small interfering RNA 3'-end overhangs on chemosensitivity to thymidylate synthase inhibitors.Silence · 2011Article
- Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells.Cancer science · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymidylate synthase (TS) is the enzyme that catalyses the last step in de novo thymidylate synthesis. It is of interest clinically because it is an effective target for drugs such as 5-fluorouracil, often used in combination therapy. Despite a number of earlier reports indicating that TS is a cell cycle-dependent enzyme, this remains equivocal. Here, we show that in HCT116 cells synchronised by serum starvation, there is a clear dissociation between the expression of cyclin E (a well-characterised cell-cycle protein) and TS. Although both cyclin E and TS mRNA and protein increased during G(1), TS upregulation was delayed. Moreover, TS levels did not decrease following S-phase completion while cyclin E decreased sharply. Similarly, clear differences were seen between cyclin E and TS as asynchronously growing HCT116 cells were growth-inhibited by low-serum treatment. In contrast to previous reports using rodent cells, adenovirus-mediated over-expression of E2F1 and cyclin E in three human cell lines had no effect on TS. Cell-cycle progression was blocked by treatment of cells with pharmacological inhibitors of CDK2 and CDK4 and by ectopic expression of p16INK4A. Whereas CDK2 inhibition had no effect on TS levels, inhibition of CDK4 was associated with decreased TS protein levels. These results provide the first evidence that drugs targeting CDK4 may be useful with anti-TS drugs as combination therapy for cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.