Evidence map›Paper›PMID 23705924›Full record

ArticleBreast cancer research : BCR2013

Amphiregulin mediates progesterone-induced mammary ductal development during puberty.

Mark D Aupperlee, Jeffrey R Leipprandt, Jessica M Bennett, Richard C Schwartz, Sandra Z Haslam

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
4.4field-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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Molecular Regulatory Mechanisms of Mammary Gland Development: A Review.Animals : an open access journal from MDPI · 2025
    Review
  4. Adult withdrawal of long-term Benzophenone-3 treatment induces regression of mammary ductal branching in a diet-dependent manner.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. 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

5 authors at 1 institution in 1 country.

Mark D Aupperlee
Jeffrey R Leipprandt
Jessica M Bennett
Richard C Schwartz
Sandra Z Haslam
Michigan State University · US

Funding

Pubertal high fat diet: effects on inflammation, mammary development and cancerU01ES019434 · NIEHS · MICHIGAN STATE UNIVERSITY · PI HASLAM, SANDRA Z · 2010 to 2014
$2.3M
NIEHS NIH HHS U01 ES019434PHS HHS 1 U01 ESO1943
6 · The paper itself

Abstract

introductionPuberty is a period of increased susceptibility to factors that cause increased breast cancer risk in adulthood. Mammary end buds (EBs) that develop during puberty are believed to be the targets of breast cancer initiation. Whereas the role of estrogen (E) has been extensively studied in pubertal mammary gland development, the role of progesterone (P) during puberty is less defined.

methodsPubertal and prepubertal ovariectomized mice were treated with vehicle control (C), E, P, or E+P. Mammary glands from these mice were analyzed for changes in morphology, proliferation, and expression of the downstream targets amphiregulin (AREG) and receptor activator of NF-κB ligand (RANKL).

resultsP, acting specifically through the progesterone receptor, induced increases in mammary gland proliferation and EB formation that were associated with increased AREG expression in ducts and EBs. E, acting specifically through the estrogen receptor, produced similar responses also mediated by AREG. Blocking AREG action by treatment with an EGFR inhibitor completely abrogated the effect of P on EB formation and proliferation and significantly reduced proliferation within ducts. P also increased expression of RANKL, primarily in ducts. Treatment with RANK-Fc, an inhibitor of RANKL, reduced P-dependent proliferation in ducts and to a lesser extent in EB, but did not cause EB regression.

conclusionsThese results demonstrate a novel P-specific effect through AREG to cause EB formation and proliferation in the developing mammary gland both before and during puberty. Thus, hormones and/or factors in addition to E that upregulate AREG can promote mammary gland development and have the potential to affect breast cancer risk associated with pubertal mammary gland development.

Indexed as

AmphiregulinAnimalsCell ProliferationEstrogensFemaleGene Expression Regulation, NeoplasticHumansMammary Glands, AnimalMiceOvariectomyProgesteronePubertyRANK LigandRisk FactorsAmphiregulinEstrogensProgesteroneRANK LigandTnfsf11 protein, mouse

Identifiers

PMID23705924
PMCPMC3738150
OpenAlexW2126588008

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.