Evidence map›Paper›PMID 22576212›Full record

ArticleCancer discovery2012

Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women.

Kotha Subbaramaiah, Patrick G Morris, Xi Kathy Zhou, Monica Morrow, Baoheng Du, Dilip Giri, Levy Kopelovich, Clifford A Hudis, Andrew J Dannenberg

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer discovery, 2012. 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 It has been retracted, and should not be counted.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 138 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 2 pooled it
18.0field-weighted citation impact, top 1% 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

138 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.

  1. Pooled it
  2. Effect ofJournal of nutritional science
    Pooled it
  3. Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  4. Trial
  5. Nonsteroidal Anti-Inflammatory Drug and Aspirin Use in Relation to Lung Cancer Risk among Postmenopausal Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015
    Trial
  6. Trial
  7. Trial
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. 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
  18. Review
  19. Review
  20. Regulation of aromatase in cancer.Molecular and cellular biochemistry · 2021
    Review

78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Kotha SubbaramaiahDepartment of Medicine, Weill Cornell Medical College, New York, New York 10065, USA. ksubba@med.cornell.edu
Patrick G Morris
Xi Kathy Zhou
Monica Morrow
Baoheng Du
Dilip Giri
Levy Kopelovich
Clifford A Hudis
Andrew J Dannenberg
Cornell University · USNational Cancer Institute · USMemorial Sloan Kettering Cancer Center · US

Funding

Targeting the Obesity-Inflammation-COX-Aromatase Axis to Lower Breast Cancer RiskR01CA154481 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DANNENBERG, ANDREW JESS · 2011 to 2015
$1.7M
NCI NIH HHS 1R01CA154481NCI NIH HHS N01 CN043302NCI NIH HHS N01-CN-43302NCI NIH HHS R01 CA154481
6 · The paper itself

Abstract

unlabelledObesity is a risk factor for hormone receptor-positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We previously showed that aromatase expression and activity are increased in the breast tissue of overweight and obese women in the presence of characteristic inflammatory foci [crown-like structures of the breast (CLS-B)]. In preclinical studies, proinflammatory prostaglandin E(2) (PGE(2)) is a determinant of aromatase expression. We provide evidence that cyclooxygenase (COX)-2-derived PGE(2) stimulates the cyclic AMP (cAMP) → PKA signal transduction pathway that activates CYP19 transcription, resulting in increased aromatase expression and elevated progesterone receptor levels in breast tissues from overweight and obese women. We further demonstrate that a measure of in-breast inflammation (CLS-B index) is a better correlate of these biologic end points than body mass index. The obesity → inflammation → aromatase axis is likely to contribute to the increased risk of hormone receptor-positive breast cancer and the worse prognosis of obese patients with breast cancer. SIGNIFICANCE: We show that obesity-associated inflammatory foci in the human breast are associated with elevated COX-2 levels and activation of the PGE2 → cAMP → PKA signal transduction pathway resulting in increased aromatase expression. These findings help to explain the link among obesity, low-grade chronic inflammation, and breast cancer with important clinical implications.

Indexed as

AdultAgedAromataseCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2DinoprostoneFemaleGene Expression RegulationHumansInflammationMammary Glands, HumanMiddle AgedObesityPromoter Regions, GeneticReceptors, ProgesteroneAromataseCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2DinoprostoneReceptors, ProgesteroneRNA, Messenger

Identifiers

PMID22576212
PMCPMC3398487
OpenAlexW2171087521

What OpenQuestion holds

Textmetadata
LicenceTDM
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.