Evidence map›Paper›PMID 24469035›Full record

ArticleOncogene2015

Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes.

A R Daniel, A L Gaviglio, T P Knutson, J H Ostrander, A B D'Assoro, P Ravindranathan, Y Peng, G V Raj, D Yee, C A Lange

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
11.0field-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

91 citing papers in PubMed, 135 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Hormone Signaling in Breast Development and Cancer.Advances in experimental medicine and biology · 2025
    Review
  7. Article
  8. Article
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  11. Review
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  18. Article
  19. Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2022
    Article
  20. Article

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

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

10 authors at 3 institutions in 1 country.

A R DanielDepartments of Medicine and Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
A L GaviglioDepartments of Medicine and Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
T P KnutsonDepartments of Medicine and Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
J H OstranderDepartment of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
A B D'AssoroDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.
P RavindranathanDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Y PengDepartment of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
G V RajDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
D YeeDepartments of Medicine and Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
C A LangeDepartments of Medicine and Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota Medical Center · USThe University of Texas Southwestern Medical Center · USMayo Clinic · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
TARGETING THE IGF SYSTEM IN BREAST CANCERR01CA074285 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI YEE, DOUGLAS · 1998 to 2012
$4.0M
Role of Phospho-Progesterone Receptors (PR) in Hormone Refractory Breast CancerR01CA159712 · NCI · UNIVERSITY OF MINNESOTA · PI LANGE, CAROL A · 2012 to 2016
$1.9M
Does Cytoplasmic PELP1 Predict Resistance To Tamoxifen Chemoprevention?K07CA131501 · NCI · UNIVERSITY OF MINNESOTA · PI OSTRANDER, JULIE H · 2010 to 2014
$580k
NCI NIH HHS K07 CA131501NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA074285NCI NIH HHS R01 CA159712
6 · The paper itself

Abstract

Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.

Indexed as

Breast NeoplasmsCathepsin DCell ProliferationCo-Repressor ProteinsDNAEstradiolEstrogen Receptor alphaFemaleHumansInsulin-Like Growth Factor IMCF-7 CellsPhosphatidylinositol 3-KinasesProtein Structure, TertiaryReceptor Cross-TalkReceptor, IGF Type 1Receptors, ProgesteroneCathepsin DCo-Repressor ProteinsCTSD protein, humanDNAESR1 protein, humanEstradiolEstrogen Receptor alphaInsulin-Like Growth Factor IPELP1 protein, humanPhosphatidylinositol 3-Kinasesprogesterone receptor BReceptor, IGF Type 1Receptors, ProgesteroneTamoxifenTranscription Factors

Identifiers

PMID24469035
PMCPMC4112172
OpenAlexW1968162784

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.