Evidence map›Paper›PMID 25615818›Full record

ArticleBiochimica et biophysica acta2015

Functional cyclic AMP response element in the breast cancer resistance protein (BCRP/ABCG2) promoter modulates epidermal growth factor receptor pathway- or androgen withdrawal-mediated BCRP/ABCG2 transcription in human cancer cells.

Yi Xie, Takeo Nakanishi, Karthika Natarajan, Lowell Safren, Anne W Hamburger, Arif Hussain, Douglas D Ross

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

Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021
    Review
  6. What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. 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

7 authors at 3 institutions in 3 countries.

Yi XieGreenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Takeo NakanishiDepartment of Membrane Transport and Biopharmaceutics, School of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Karthika NatarajanGreenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Lowell SafrenSchnaper Summer Internship Program, University of Maryland Greenebaum Cancer Center, USA.
Anne W HamburgerGreenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Arif HussainGreenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Baltimore VA Medical Center, Baltimore, MD 21201, USA.
Douglas D RossGreenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Baltimore VA Medical Center, Baltimore, MD 21201, USA; Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: dross@som.umaryland.edu.
University of Maryland, Baltimore · USKanazawa University · JPUniversidade de Itaúna · BR

Funding

A Novel Mechanism for Control of Androgen Receptor Levels in HRPCR01CA138583 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI HAMBURGER, ANNE W. · 2011 to 2013
$824k
NCI NIH HHS 1R01CA138583NCI NIH HHS R01 CA138583
6 · The paper itself

Abstract

Phosphorylated cyclic-AMP (cAMP) response element binding protein (p-CREB) is a downstream effector of a variety of important signaling pathways. We investigated whether the human BCRP promoter contains a functional cAMP response element (CRE). 8Br-cAMP, a cAMP analogue, increased the activity of a BCRP promoter reporter construct and BCRP mRNA in human carcinoma cells. Epidermal growth factor receptor (EGFR) pathway activation also led to an increase in p-CREB and in BCRP promoter reporter activity via two major downstream EGFR signaling pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway. EGF treatment increased the phosphorylation of EGFR, AKT, ERK and CREB, while simultaneously enhancing BCRP mRNA and functional protein expression. EGF-stimulated CREB phosphorylation and BCRP induction were diminished by inhibition of EGFR, PI3K/AKT or RAS/MAPK signaling. CREB silencing using RNA interference reduced basal levels of BCRP mRNA and diminished the induction of BCRP by EGF. Chromatin immunoprecipitation assays confirmed that a putative CRE site on the BCRP promoter bound p-CREB by a point mutation of the CRE site abolished EGF-induced stimulation of BCRP promoter reporter activity. Furthermore, the CREB co-activator, cAMP-regulated transcriptional co-activator (CRTC2), is involved in CREB-mediated BCRP transcription: androgen depletion of LNCaP human prostate cancer cells increased both CREB phosphorylation and CRTC2 nuclear translocation, and enhanced BCRP expression. Silencing CREB or CRTC2 reduced basal BCRP expression and BCRP induction under androgen-depletion conditions. This novel CRE site plays a central role in mediating BCRP gene expression in several human cancer cell lines following activation of multiple cancer-relevant signaling pathways.

Indexed as

Transcription, GeneticAndrogensATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Breast NeoplasmsCell Line, TumorCyclic AMPCyclic AMP Response Element-Binding ProteinErbB ReceptorsFemaleGene Expression Regulation, NeoplasticHumansMaleNeoplasm ProteinsOvarian NeoplasmsPhosphorylationABCG2 protein, humanAndrogensATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CRTC2 protein, humanCyclic AMPCyclic AMP Response Element-Binding ProteinEGFR protein, humanErbB ReceptorsNeoplasm ProteinsTranscription FactorsBreast cancerBreast cancer resistance protein (BCRP)/ABCG2CREBOvarian cancerPromoterProstate cancer

Identifiers

PMID25615818
PMCPMC4336604
OpenAlexW2009683766

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.