Evidence map›Paper›PMID 18083712›Full record

ArticleThe Journal of biological chemistry2008

EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange.

Kotha Subbaramaiah, Clifford Hudis, Sung-Hee Chang, Timothy Hla, Andrew J Dannenberg

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Publisher
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.3field-weighted citation impact, top 5% 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

45 citing papers in PubMed, 89 citations in OpenAlex.

  1. Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022
    Review
  2. Article
  3. Article
  4. Prostaglandin EThe Journal of biological chemistry · 2019
    Article
  5. Review
  6. The Impact of Obesity on Breast Cancer.Current oncology reports · 2018
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Obesity and Cancer: Concepts and Challenges.Indian journal of surgical oncology · 2015
    Article
  12. Estrogen Protects against Obesity-Induced Mammary Gland Inflammation in Mice.Cancer prevention research (Philadelphia, Pa.) · 2015
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Kotha SubbaramaiahDepartment of Medicine, Weill Cornell Medical College, New York, New York 10065. Electronic address: ksubba@med.cornell.edu.
Clifford HudisDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
Sung-Hee ChangCenter for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3501.
Timothy HlaCenter for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3501.
Andrew J DannenbergDepartment of Medicine, Weill Cornell Medical College, New York, New York 10065.
Cornell University · USUConn Health · USMemorial Sloan Kettering Cancer Center · US

Funding

THE ROLE OF ENDOCANNABINOIDS AND THEIR RECEPTORS IN COLORECTAL CANCERP01CA077839 · NCI · VANDERBILT UNIVERSITY · PI DUBOIS, RAYMOND N. · 1999 to 2016
$17.8M
NCI NIH HHS P01CA77839
6 · The paper itself

Abstract

Cytochrome P450 aromatase (aromatase), a product of the CYP19 gene, catalyzes the synthesis of estrogens from androgens. Because aromatase-dependent estrogen biosynthesis has been linked to hormone-dependent breast carcinogenesis, it is important to elucidate the mechanisms that regulate CYP19 gene expression. The main objective of this study was to identify the receptors (EP) for prostaglandin E(2) (PGE(2)) that mediate the induction of CYP19 transcription in human adipocytes and breast cancer cells. Treatment with PGE(2) induced aromatase, an effect that was mimicked by either EP(2) or EP(4) agonists. Antagonists of EP(2) or EP(4) or small interference RNA-mediated down-regulation of these receptors suppressed PGE(2)-mediated induction of aromatase. PGE(2) via EP(2) and EP(4) stimulated the cAMP-->protein kinase A pathway resulting in enhanced interaction between P-CREB, p300, and the aromatase promoter I.3/II. Overexpressing a mutant form of p300 that lacks histone acetyltransferase activity suppressed PGE(2)-mediated induction of aromatase promoter activity. PGE(2) via EP(2) and EP(4) also caused a reduction in both the amounts of BRCA1 and the interaction between BRCA1 and the aromatase promoter I.3/II. Activation of the aromatase promoter by PGE(2) was suppressed by overexpressing wild-type BRCA1. Silencing of EP(2) or EP(4) also blocked PGE(2)-mediated induction of the progesterone receptor, a prototypic estrogen-response gene. In a mouse model, overexpressing COX-2 in the mammary gland, a known inducer of PGE(2) synthesis, led to increased aromatase mRNA and activity and reduced amounts of BRCA1; these effects were reversed by knocking out EP(2). Taken together, these results suggest that PGE(2) via EP(2) and EP(4) activates the cAMP-->PKA-->CREB pathway leading to enhanced CYP19 transcription and increased aromatase activity. Reciprocal changes in the interaction between BRCA1, p300, and the aromatase promoter I.3/II contributed to the inductive effects of PGE(2).

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticAdipocytesAnimalsAromataseBRCA1 ProteinBreast NeoplasmsCell Line, TumorDinoprostoneE1A-Associated p300 ProteinHumansMammary Neoplasms, AnimalMiceMice, TransgenicReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeAromataseBRCA1 ProteinBRCA1 protein, humanDinoprostoneE1A-Associated p300 ProteinEP300 protein, humanPTGER2 protein, humanPtger2 protein, mousePTGER4 protein, humanPtger4 protein, mouseReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 Subtype

Identifiers

PMID18083712
OpenAlexW1963685103

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.