Evidence map›Paper›PMID 26206332›Full record

ArticleMolecular cancer therapeutics2015

Silencing Egr1 Attenuates Radiation-Induced Apoptosis in Normal Tissues while Killing Cancer Cells and Delaying Tumor Growth.

Diana Yi Zhao, Keith M Jacobs, Dennis E Hallahan, Dinesh Thotala

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. EGR1 Addiction in Diffuse Large B-cell Lymphoma.Molecular cancer research : MCR · 2021
    Article
  5. Observational
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Effect of MMP-2 gene silencing on radiation-induced DNA damage in human normal dermal fibroblasts and breast cancer cells.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2019
    Article
  14. Article
  15. Mithramycin A Enhances Tumor Sensitivity to Mitotic Catastrophe Resulting From DNA Damage.International journal of radiation oncology, biology, physics · 2018
    Article
  16. Article
  17. Review
  18. Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter.Journal of experimental & clinical cancer research : CR · 2017
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Diana Yi ZhaoDepartment of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Keith M JacobsDepartment of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Dennis E HallahanDepartment of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, Missouri. Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Dinesh ThotalaDepartment of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, Missouri. dthotala@radonc.wustl.edu.
Washington University in St. Louis · US

Funding

NATIONAL RESEARCH SERVICE AWARD-MEDICAL SCIENTISTT32GM007200 · NIGMS · WASHINGTON UNIVERSITY · PI YOKOYAMA, WAYNE M. · 1985 to 2024
$59.8M
THE ROLE OF PROTEIN PHOSPHATASE PP2A IN RADIATION INDUCED STEM CELL APOPTOSISR01CA174966 · NCI · WASHINGTON UNIVERSITY · PI HALLAHAN, DENNIS E, SHARMA, GIRDHAR GOPAL · 2013 to 2017
$2.3M
NCI NIH HHS 5R01CA174966-03NCI NIH HHS R01 CA174966NIGMS NIH HHS 5T32 GM07200NIGMS NIH HHS T32 GM007200
6 · The paper itself

Abstract

Normal tissue toxicity reduces the therapeutic index of radiotherapy and decreases the quality of life for cancer survivors. Apoptosis is a key element of the radiation response in normal tissues like the hippocampus and small intestine, resulting in neurocognitive disorders and intestinal malabsorption. The Early Growth Response 1 (Egr1) transcription factor mediates radiation-induced apoptosis by activating the transcription of proapoptosis genes in response to ionizing radiation (IR). Therefore, we hypothesized that the genetic abrogation of Egr1 and the pharmacologic inhibition of its transcriptional activity could attenuate radiation-induced apoptosis in normal tissues. We demonstrated that Egr1-null mice had less apoptosis in the hippocampus and intestine following irradiation as compared with their wild-type littermates. A similar result was achieved using Mithramycin A (MMA) to prevent binding of Egr1 to target promoters in the mouse intestine. Abolishing Egr1 expression using shRNA dampened apoptosis and enhanced the clonogenic survival of irradiated HT22 hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically, these events involved an abrogation of p53 induction by IR and an increase in the ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two cancer cell lines (GL261 glioma cells and HCT116 colorectal cancer cells) was not radioprotective, since it reduced their growth while also sensitizing them to radiation-induced death. Further, Egr1 depletion delayed the growth of heterotopically implanted GL261 and HCT116 tumors. These results support the potential of silencing Egr1 in order to minimize the normal tissue complications associated with radiotherapy while enhancing tumor control.

Indexed as

AnimalsApoptosisCell ProliferationCell SurvivalEarly Growth Response Protein 1Gene Knockdown TechniquesGene SilencingHCT116 CellsHippocampusHumansIntestine, SmallMice, Inbred C57BLRadiation Injuries, ExperimentalRadiation ToleranceRNA InterferenceRNA, Small InterferingEarly Growth Response Protein 1EGR1 protein, humanRNA, Small Interfering

Identifiers

PMID26206332
PMCPMC4845655
OpenAlexW1934889082

What OpenQuestion holds

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Registered trials

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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.