Here's how NATURE.COM makes money* and how much!

*Please read our disclaimer before using our estimates.
Loading...

NATURE . COM {}

  1. Analyzed Page
  2. Matching Content Categories
  3. CMS
  4. Monthly Traffic Estimate
  5. How Does Nature.com Make Money
  6. How Much Does Nature.com Make
  7. Keywords
  8. Topics
  9. Questions
  10. Schema
  11. Social Networks
  12. External Links
  13. Analytics And Tracking
  14. Libraries
  15. Hosting Providers
  16. CDN Services

We are analyzing https://www.nature.com/articles/4401000.

Title:
Ligand activation of peroxisome proliferator-activated receptor γ induces apoptosis of leukemia cells by down-regulating the c-myc gene expression via blockade of the Tcf-4 activity | Cell Death & Differentiation
Description:
The peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is expressed at highest levels in adipose tissue and functions as a central regulator in the process of adipocyte differentiation. In the present study, we showed that human leukemic cell lines, not only myeloid but also lymphoid, express PPAR γ and its activation by natural ligand (15-deoxy-Δ12,14 - prostaglandin J2) and synthetic ligand (troglitazone) profoundly inhibited their proliferation by induction of apoptosis preferentially in the serum-free culture. We pursued its mechanism using the representative cell lines, and found that induction of apoptosis was accompanied by caspase-3 activation and specifically blocked by its inhibitor. While status of several apoptosis-related molecules remained unchanged, the c-Myc expression was markedly down-regulated within 24 h after troglitazone treatment. The c-myc mRNA levels were dramatically reduced at 1 h and became undetectable at 12 h after troglitazone treatment, which proved to be accompanied by complete blockade of the Tcf-4 activity in the electrophoretic mobility shift assay. We succeeded in establishing HL-60 cell lines growing well in the presence of troglitazone in the long-term serum-free culture. They showed neither induction of apoptosis nor down-regulation of the c-Myc expression via blockade of the Tcf-4 activity after troglitazone treatment. This is the first identification of the linkage between PPAR γ-mediated apoptosis and down-regulation of the c-myc gene expression.
Website Age:
30 years and 10 months (reg. 1994-08-11).

Matching Content Categories {📚}

  • Science
  • Education
  • Telecommunications

Content Management System {📝}

What CMS is nature.com built with?

Custom-built

No common CMS systems were detected on Nature.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of nature.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Nature.com Make Money? {💸}


Display Ads {🎯}


The website utilizes display ads within its content to generate revenue. Check the next section for further revenue estimates.

Ads are managed by yourbow.com. Particular relationships are as follows:

Direct Advertisers (10)
google.com, pmc.com, doceree.com, yourbow.com, audienciad.com, onlinemediasolutions.com, advibe.media, aps.amazon.com, getmediamx.com, onomagic.com

Reseller Advertisers (38)
conversantmedia.com, rubiconproject.com, pubmatic.com, appnexus.com, openx.com, smartadserver.com, lijit.com, sharethrough.com, video.unrulymedia.com, google.com, yahoo.com, triplelift.com, onetag.com, sonobi.com, contextweb.com, 33across.com, indexexchange.com, media.net, themediagrid.com, adform.com, richaudience.com, sovrn.com, improvedigital.com, freewheel.tv, smaato.com, yieldmo.com, amxrtb.com, adyoulike.com, adpone.com, criteo.com, smilewanted.com, 152media.info, e-planning.net, smartyads.com, loopme.com, opera.com, mediafuse.com, betweendigital.com

How Much Does Nature.com Make? {💰}


Display Ads {🎯}

$63,100 per month
Our estimates place Nature.com's monthly online earnings from display ads at $42,042 to $115,616.

Keywords {🔍}

cell, troglitazone, cells, cmyc, ppar, expression, μgml, google, scholar, article, lanes, apoptosis, cas, tcf, activation, treatment, lines, dmemf, figure, activity, shown, receptor, lane, cultured, resistant, presence, leukemia, downregulation, peroxisome, culture, nature, antibody, medium, nuclear, line, concentrations, differentiation, human, inhibition, fcs, nfκb, data, ligand, proliferatoractivated, dna, induces, induction, open, addition, caspase,

Topics {✒️}

n-benzyloxycarbonyl-asp-glu-val-asp-fluoromethylketone nature portfolio permissions reprints privacy policy macrophage nature 391 peroxisome proliferator-activated receptor-γ receptors nature 358 advertising fcs-free d-mem/f12 medium c-myc proto-oncogene product long-term serum-free culture peroxisome proliferator-activated receptor selective inhibitor z-devd-fmk peroxisome proliferator-activated receptors social media wright–giemsa staining nature 10% fcs-d-mem/f12 medium ccaat/enhancer-binding protein α proliferator-activated receptors α peroxisome-proliferated receptor γ author correspondence human monocyte-derived macrophages middle full-scaled ligand activation apc/β-catenin/tcf-4 pathway map kinase-mediated phosphorylation murine b-lymphoma cells ligand-activated transcription factors repress mir-28-5p/ezh2 d-mem/f12 medium c-myc promoter proc c-myc gene product viral oncogene v-myc c-myc proto-oncogene protein a-sepharose beads α-32p-dctp-labeled 1 human c-myc promoter peroxisomal β-oxidation pathway oncogene-induced replication stress zinc-inducible expression plasmids b-lymphoid cell lines oral anti-diabetic agents transmit anti-apoptotic signal 32p-labeled tcf-4 oligonucleotide murine c-myc promoter anti-ppar γ antibody counteracting anti-apoptotic proteins nf-κb p65 subunit c-myc gene expression

Questions {❓}

  • 1998 PPAR γ in monocytes: less pain, any gain?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Ligand activation of peroxisome proliferator-activated receptor γ induces apoptosis of leukemia cells by down-regulating the c-myc gene expression via blockade of the Tcf-4 activity
         description:The peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is expressed at highest levels in adipose tissue and functions as a central regulator in the process of adipocyte differentiation. In the present study, we showed that human leukemic cell lines, not only myeloid but also lymphoid, express PPAR γ and its activation by natural ligand (15-deoxy-Δ12,14 - prostaglandin J2) and synthetic ligand (troglitazone) profoundly inhibited their proliferation by induction of apoptosis preferentially in the serum-free culture. We pursued its mechanism using the representative cell lines, and found that induction of apoptosis was accompanied by caspase-3 activation and specifically blocked by its inhibitor. While status of several apoptosis-related molecules remained unchanged, the c-Myc expression was markedly down-regulated within 24 h after troglitazone treatment. The c-myc mRNA levels were dramatically reduced at 1 h and became undetectable at 12 h after troglitazone treatment, which proved to be accompanied by complete blockade of the Tcf-4 activity in the electrophoretic mobility shift assay. We succeeded in establishing HL-60 cell lines growing well in the presence of troglitazone in the long-term serum-free culture. They showed neither induction of apoptosis nor down-regulation of the c-Myc expression via blockade of the Tcf-4 activity after troglitazone treatment. This is the first identification of the linkage between PPAR γ-mediated apoptosis and down-regulation of the c-myc gene expression.
         datePublished:2002-04-25T00:00:00Z
         dateModified:2002-04-25T00:00:00Z
         pageStart:513
         pageEnd:526
         sameAs:https://doi.org/10.1038/sj.cdd.4401000
         keywords:
            PPAR γ
            apoptosis
            leukemia cells
            c-myc
            Tcf-4
            Life Sciences
            general
            Biochemistry
            Cell Biology
            Stem Cells
            Apoptosis
            Cell Cycle Analysis
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig1_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig2_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig3_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig4_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig5_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig6_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig7_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig8_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig9_HTML.jpg
         isPartOf:
            name:Cell Death & Differentiation
            issn:
               1476-5403
               1350-9047
            volumeNumber:9
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Nature Publishing Group UK
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:N Yamakawa-Karakida
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:K Sugita
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
               name:T Inukai
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:K Goi
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:M Nakamura
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:K Uno
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:H Sato
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:K Kagami
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
               name:N Barker
               affiliation:
                     name:University Hospital Utrecht
                     address:
                        name:Department of Immunology, University Hospital Utrecht, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:S Nakazawa
               affiliation:
                     name:Yamanashi Medical University
                     address:
                        name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                        type:PostalAddress
                     type:Organization
               type:Person
         isAccessibleForFree:1
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Ligand activation of peroxisome proliferator-activated receptor γ induces apoptosis of leukemia cells by down-regulating the c-myc gene expression via blockade of the Tcf-4 activity
      description:The peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is expressed at highest levels in adipose tissue and functions as a central regulator in the process of adipocyte differentiation. In the present study, we showed that human leukemic cell lines, not only myeloid but also lymphoid, express PPAR γ and its activation by natural ligand (15-deoxy-Δ12,14 - prostaglandin J2) and synthetic ligand (troglitazone) profoundly inhibited their proliferation by induction of apoptosis preferentially in the serum-free culture. We pursued its mechanism using the representative cell lines, and found that induction of apoptosis was accompanied by caspase-3 activation and specifically blocked by its inhibitor. While status of several apoptosis-related molecules remained unchanged, the c-Myc expression was markedly down-regulated within 24 h after troglitazone treatment. The c-myc mRNA levels were dramatically reduced at 1 h and became undetectable at 12 h after troglitazone treatment, which proved to be accompanied by complete blockade of the Tcf-4 activity in the electrophoretic mobility shift assay. We succeeded in establishing HL-60 cell lines growing well in the presence of troglitazone in the long-term serum-free culture. They showed neither induction of apoptosis nor down-regulation of the c-Myc expression via blockade of the Tcf-4 activity after troglitazone treatment. This is the first identification of the linkage between PPAR γ-mediated apoptosis and down-regulation of the c-myc gene expression.
      datePublished:2002-04-25T00:00:00Z
      dateModified:2002-04-25T00:00:00Z
      pageStart:513
      pageEnd:526
      sameAs:https://doi.org/10.1038/sj.cdd.4401000
      keywords:
         PPAR γ
         apoptosis
         leukemia cells
         c-myc
         Tcf-4
         Life Sciences
         general
         Biochemistry
         Cell Biology
         Stem Cells
         Apoptosis
         Cell Cycle Analysis
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig1_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig2_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig3_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig4_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig5_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig6_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig7_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig8_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fsj.cdd.4401000/MediaObjects/41418_2002_Article_BF4401000_Fig9_HTML.jpg
      isPartOf:
         name:Cell Death & Differentiation
         issn:
            1476-5403
            1350-9047
         volumeNumber:9
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Nature Publishing Group UK
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:N Yamakawa-Karakida
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:K Sugita
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:T Inukai
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:K Goi
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:M Nakamura
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:K Uno
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:H Sato
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:K Kagami
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
            name:N Barker
            affiliation:
                  name:University Hospital Utrecht
                  address:
                     name:Department of Immunology, University Hospital Utrecht, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:S Nakazawa
            affiliation:
                  name:Yamanashi Medical University
                  address:
                     name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
                     type:PostalAddress
                  type:Organization
            type:Person
      isAccessibleForFree:1
["Periodical","PublicationVolume"]:
      name:Cell Death & Differentiation
      issn:
         1476-5403
         1350-9047
      volumeNumber:9
Organization:
      name:Nature Publishing Group UK
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
      name:University Hospital Utrecht
      address:
         name:Department of Immunology, University Hospital Utrecht, The Netherlands
         type:PostalAddress
      name:Yamanashi Medical University
      address:
         name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:N Yamakawa-Karakida
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:K Sugita
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:T Inukai
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:K Goi
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:M Nakamura
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:K Uno
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:H Sato
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:K Kagami
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
      name:N Barker
      affiliation:
            name:University Hospital Utrecht
            address:
               name:Department of Immunology, University Hospital Utrecht, The Netherlands
               type:PostalAddress
            type:Organization
      name:S Nakazawa
      affiliation:
            name:Yamanashi Medical University
            address:
               name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan
      name:Department of Immunology, University Hospital Utrecht, The Netherlands
      name:Department of Pediatrics, Yamanashi Medical University, Yamanashi, Japan

Social Networks {👍}(1)

External Links {🔗}(159)

Analytics and Tracking {📊}

  • Google Tag Manager

Libraries {📚}

  • Prism.js
  • Zoom.js

Emails and Hosting {✉️}

Mail Servers:

  • mxa-002c5801.gslb.pphosted.com
  • mxb-002c5801.gslb.pphosted.com

Name Servers:

  • pdns1.ultradns.net
  • pdns2.ultradns.net
  • pdns3.ultradns.org
  • pdns4.ultradns.org
  • pdns5.ultradns.info
  • pdns6.ultradns.co.uk

CDN Services {📦}

  • Crossref

4.61s.