Evidence map›Paper›PMID 20123965›Full record

ArticleMolecular and cellular biology2010

Multimodal regulation of E2F1 gene expression by progestins.

Hilary E Wade, Sakiko Kobayashi, Matthew L Eaton, Michelle S Jansen, Edward K Lobenhofer, Mathieu Lupien, Timothy R Geistlinger, Wencheng Zhu, Joseph R Nevins, Myles Brown and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Uterine ALK3 is essential during the window of implantation.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  7. KLF15 in breast cancer: a novel tumor suppressor?Cellular oncology (Dordrecht, Netherlands) · 2015
    Article
  8. Article
  9. Krüppel-like factors are effectors of nuclear receptor signaling.General and comparative endocrinology · 2014
    Review
  10. Article
  11. Article
  12. Article
  13. Treatment for Uterine Fibroids: Searching for Effective Drug Therapies.Drug discovery today. Therapeutic strategies · 2012
    Article
  14. Article
  15. Article
  16. Article
  17. 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

12 authors at 4 institutions in 1 country.

Hilary E WadeDuke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA.
Sakiko Kobayashi
Matthew L Eaton
Michelle S Jansen
Edward K Lobenhofer
Mathieu Lupien
Timothy R Geistlinger
Wencheng Zhu
Joseph R Nevins
Myles Brown
Deborah C Otteson
Donald P McDonnell
Duke University Hospital · USDana-Farber Cancer Institute · USDuke University · USUniversity of Houston · US

Funding

Use of Organotypic and Mammary Gland Models to Investigate the Outcomes of ClonalP01CA080111 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI DILLON, DEBORAH · 1999 to 2018
$36.0M
Variation in Receptor Tyrosine Kinases and Breast Cancer RiskP50CA089393 · NCI · DANA-FARBER CANCER INSTITUTE · PI HARRIS, LYNDSAY NORINE · 2000 to 2009
$28.8M
Mechanism of Action of Estrogens and AntiestrogensR37DK048807 · NIDDK · DUKE UNIVERSITY · PI MCDONNELL, DONALD P · 2005 to 2014
$5.0M
MECHANISM OF ESTROGENS AND ANTIESTROGENSR01DK048807 · NIDDK · DUKE UNIVERSITY · PI MCDONNELL, DONALD P · 1995 to 2019
$4.3M
Comprehensive Analysis of Estrogen Receptor Genomic ActionR01DK074967 · NIDDK · DANA-FARBER CANCER INST · PI BROWN, MYLES A · 2007 to 2011
$2.9M
Comprehensive Analysis of Estrogen Receptor Genomic ActionR56DK074967 · NIDDK · DANA-FARBER CANCER INST · PI BROWN, MYLES A · 2006 to 2006
$420k
Regulation of Rhodopsin Expression: The Role of RKLFF32EY013499 · NEI · JOHNS HOPKINS UNIVERSITY · PI OTTESON, DEBORAH C · 2001 to 2002
$79k
NCI NIH HHS CA080111NCI NIH HHS CA089393NCI NIH HHS P01 CA080111NCI NIH HHS P50 CA089393NEI NIH HHS EY13499NEI NIH HHS F32 EY013499NIDDK NIH HHS DK048807NIDDK NIH HHS DK074967NIDDK NIH HHS R01 DK048807NIDDK NIH HHS R01 DK074967NIDDK NIH HHS R37 DK048807NIDDK NIH HHS R56 DK074967
6 · The paper itself

Abstract

An analysis of mRNA expression in T47D breast cancer cells treated with the synthetic progestin R5020 revealed a subset of progesterone receptor (PR) target genes that are enriched for E2F binding sites. Following up on this observation, we determined that PR-B acts in both direct and indirect manners to positively upregulate E2F1 expression in T47D cells. The direct effects of PR on E2F1 expression were confirmed by chromatin immunoprecipitation (ChIP) analysis, which indicated that the agonist-bound receptor was recruited to several enhancer elements proximal to the E2F1 transcript. However, we also noted that cycloheximide partially inhibits R5020 induction of E2F1 expression, indicating that the ligand-dependent actions of PR on this gene may involve additional indirect regulatory pathways. In support of this hypothesis, we demonstrated that treatment with R5020 significantly increases both hyperphosphorylation of Rb and recruitment of E2F1 to its own promoter, thus activating a positive feedback loop that further amplifies its transcription. Furthermore, we established that PR-mediated induction of Krüppel-like factor 15 (KLF15), which can bind to GC-rich DNA within the E2F1 promoter, is required for maximal induction of E2F1 expression by progestins. Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR.

Indexed as

Breast NeoplasmsCell Line, TumorE2F1 Transcription FactorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, ReporterHumansKruppel-Like Transcription FactorsMitogen-Activated Protein KinasesNuclear ProteinsOligonucleotide Array Sequence AnalysisPlicamycinProgestinsPromegestonePromoter Regions, GeneticE2F1 Transcription FactorKLF15 protein, humanKruppel-Like Transcription Factorsmithramycin AMitogen-Activated Protein KinasesNuclear ProteinsPlicamycinprogesterone receptor BProgestinsPromegestoneReceptors, ProgesteroneRetinoblastoma ProteinTacrolimus Binding Protein 5Tacrolimus Binding Proteins

Identifiers

PMID20123965
PMCPMC2849472
OpenAlexW2133682449

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.