We are analyzing https://link.springer.com/article/10.1186/bcr2883.

Title:
Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes | Breast Cancer Research
Description:
Introduction Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) is phosphorylated in all breast cancer subtypes. Past findings have shown that IGF-1R mediates antiestrogen resistance through cross-talk with estrogen receptor (ER) signaling and via its action upstream of the epidermal growth factor receptor and human epidermal growth factor receptor 2. Yet, the direct role of IGF-1R signaling itself in antiestrogen resistance remains obscure. In the present study, we sought to elucidate whether antiestrogen resistance is induced directly by IGF-1R signaling in response to its ligand IGF-1 stimulation. Methods A breast cancer cell line ectopically expressing human wild-type IGF-1R, MCF7/IGF-1R, was established by retroviral transduction and colony selection. Cellular antiestrogen sensitivity was evaluated under estrogen-depleted two-dimensional (2D) and 3D culture conditions. Functional activities of the key IGF-1R signaling components in antiestrogen resistance were assessed by specific kinase inhibitor compounds and small interfering RNA. Results Ectopic expression of IGF-1R in ER-positive MCF7 human breast cancer cells enhanced IGF-1R tyrosine kinase signaling in response to IGF-1 ligand stimulation. The elevated IGF-1R signaling rendered MCF7/IGF-1R cells highly resistant to the antiestrogens tamoxifen and fulvestrant. This antiestrogen-resistant phenotype involved mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B pathways downstream of the IGF-1R signaling hub and was independent of ER signaling. Intriguingly, a MAPK/ERK-dependent agonistic behavior of tamoxifen at low doses was triggered in the presence of IGF-1, showing a mild promitogenic effect and increasing ER transcriptional activity. Conclusions Our data provide evidence that the IGF-1/IGF-1R signaling axis may play a causal role in antiestrogen resistance of breast cancer cells, despite continuous suppression of ER transcriptional function by antiestrogens.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Science
Education
Health & Fitness

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

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

Traffic Estimate {📈}

What is the average monthly size of link.springer.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 Link.springer.com Make Money? {💸}

We can't see how the site brings in money.

Some websites aren't about earning revenue; they're built to connect communities or raise awareness. There are numerous motivations behind creating websites. This might be one of them. Link.springer.com could have a money-making trick up its sleeve, but it's undetectable for now.

Keywords {🔍}

cells, igfr, cancer, mcfigfr, resistance, signaling, igf, breast, figure, kinase, pubmed, google, scholar, receptor, cas, cell, ohtam, growth, proliferation, factor, antiestrogen, mcf, tamoxifen, tam, estrogen, data, expression, response, ful, ngml, insulinlike, activity, effect, phosphorylation, erα, sirna, human, inhibitor, agonistic, usa, file, mapkerk, inhibitors, antiestrogens, protein, pathways, bez, medium, akt, res,

Topics {✒️}

retroviral vector pmscv-neo-igf-1r igf-1-stimulated mcf7/igf-1r cells pmscv-neo-igf-1r vector mcf7/igf-1r cell model sustained igf-1r/mapk/pi3k signaling mcf7/igf-1r cells overruled igf-1/igf-1r signaling route 5% charcoal/dextran-stripped fbs er/her2-positive breast cancer igf-1/igf-1r signaling axis mcf7/igf-1r cells compared igf-1r signal-mediated 4 human breast-cancer cells elevated igf-1r signaling igf-1/igf-1r-driven proliferation igf/e2/tam-induced cell proliferation pmscv-neo-igf-1r mcf7/igf-1r stimulated igf-1r/erk/akt signaling mcf7 versus mcf7/insulin enhanced igf-1r signaling steroid hormone receptors igf-1r signal transduction mcf7/igf-1r cells igf-1r signaling involves tamoxifen-resistant breast cancer igf-1/igf-1r axis phosphatidylinositol 3-kinase/protein kinase ectopic igf-1r expression pi3k/akt kinases c-raf-1 pi3k/akt signaling routes rabbit anti-phospho-igf-1rβ inhibit igf-1-stimulated signaling oestrogen-receptor-mediated transcription igf-1/igf-1r signaling [49] igf-1r signaling hub igf-1r signaling network igf-1r signaling map extent igf-1r signaling half-maximal effective concentration igf-1r rtk signaling igf-1r confers resistance igf-1r inhibitor bms-536924 demonstrate igf-1r autoactivation affect ere-mediated transcription transcription factors nf-κb total igf-1r level tropix western-superstar™ procedure 293t cell-based systems igf-1r-encoding retroviruses

Questions {❓}

Dawood S, Cristofanilli M: Endocrine resistance in breast cancer: what really matters?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes
         description:Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) is phosphorylated in all breast cancer subtypes. Past findings have shown that IGF-1R mediates antiestrogen resistance through cross-talk with estrogen receptor (ER) signaling and via its action upstream of the epidermal growth factor receptor and human epidermal growth factor receptor 2. Yet, the direct role of IGF-1R signaling itself in antiestrogen resistance remains obscure. In the present study, we sought to elucidate whether antiestrogen resistance is induced directly by IGF-1R signaling in response to its ligand IGF-1 stimulation. A breast cancer cell line ectopically expressing human wild-type IGF-1R, MCF7/IGF-1R, was established by retroviral transduction and colony selection. Cellular antiestrogen sensitivity was evaluated under estrogen-depleted two-dimensional (2D) and 3D culture conditions. Functional activities of the key IGF-1R signaling components in antiestrogen resistance were assessed by specific kinase inhibitor compounds and small interfering RNA. Ectopic expression of IGF-1R in ER-positive MCF7 human breast cancer cells enhanced IGF-1R tyrosine kinase signaling in response to IGF-1 ligand stimulation. The elevated IGF-1R signaling rendered MCF7/IGF-1R cells highly resistant to the antiestrogens tamoxifen and fulvestrant. This antiestrogen-resistant phenotype involved mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B pathways downstream of the IGF-1R signaling hub and was independent of ER signaling. Intriguingly, a MAPK/ERK-dependent agonistic behavior of tamoxifen at low doses was triggered in the presence of IGF-1, showing a mild promitogenic effect and increasing ER transcriptional activity. Our data provide evidence that the IGF-1/IGF-1R signaling axis may play a causal role in antiestrogen resistance of breast cancer cells, despite continuous suppression of ER transcriptional function by antiestrogens.
         datePublished:2011-05-19T00:00:00Z
         dateModified:2011-05-19T00:00:00Z
         pageStart:1
         pageEnd:16
         sameAs:https://doi.org/10.1186/bcr2883
         keywords:
            Estrogen Receptor
            Tamoxifen
            Fulvestrant
            Parental MCF7 Cell
            Specific Kinase Inhibitor
            Cancer Research
            Oncology
            Surgical Oncology
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig1_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig2_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig3_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig4_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig5_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig6_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig7_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig8_HTML.jpg
         isPartOf:
            name:Breast Cancer Research
            issn:
               1465-542X
            volumeNumber:13
            type:
               Periodical
               PublicationVolume
         publisher:
            name:BioMed Central
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Yinghui Zhang
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Marja Moerkens
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Sreenivasa Ramaiahgari
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Hans de Bont
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Leo Price
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               type:Person
               name:John Meerman
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
               name:Bob van de Water
               affiliation:
                     name:Leiden University
                     address:
                        name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:1
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes
      description:Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) is phosphorylated in all breast cancer subtypes. Past findings have shown that IGF-1R mediates antiestrogen resistance through cross-talk with estrogen receptor (ER) signaling and via its action upstream of the epidermal growth factor receptor and human epidermal growth factor receptor 2. Yet, the direct role of IGF-1R signaling itself in antiestrogen resistance remains obscure. In the present study, we sought to elucidate whether antiestrogen resistance is induced directly by IGF-1R signaling in response to its ligand IGF-1 stimulation. A breast cancer cell line ectopically expressing human wild-type IGF-1R, MCF7/IGF-1R, was established by retroviral transduction and colony selection. Cellular antiestrogen sensitivity was evaluated under estrogen-depleted two-dimensional (2D) and 3D culture conditions. Functional activities of the key IGF-1R signaling components in antiestrogen resistance were assessed by specific kinase inhibitor compounds and small interfering RNA. Ectopic expression of IGF-1R in ER-positive MCF7 human breast cancer cells enhanced IGF-1R tyrosine kinase signaling in response to IGF-1 ligand stimulation. The elevated IGF-1R signaling rendered MCF7/IGF-1R cells highly resistant to the antiestrogens tamoxifen and fulvestrant. This antiestrogen-resistant phenotype involved mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B pathways downstream of the IGF-1R signaling hub and was independent of ER signaling. Intriguingly, a MAPK/ERK-dependent agonistic behavior of tamoxifen at low doses was triggered in the presence of IGF-1, showing a mild promitogenic effect and increasing ER transcriptional activity. Our data provide evidence that the IGF-1/IGF-1R signaling axis may play a causal role in antiestrogen resistance of breast cancer cells, despite continuous suppression of ER transcriptional function by antiestrogens.
      datePublished:2011-05-19T00:00:00Z
      dateModified:2011-05-19T00:00:00Z
      pageStart:1
      pageEnd:16
      sameAs:https://doi.org/10.1186/bcr2883
      keywords:
         Estrogen Receptor
         Tamoxifen
         Fulvestrant
         Parental MCF7 Cell
         Specific Kinase Inhibitor
         Cancer Research
         Oncology
         Surgical Oncology
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig1_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig2_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig3_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig4_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig5_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig6_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig7_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fbcr2883/MediaObjects/13058_2010_9517_Fig8_HTML.jpg
      isPartOf:
         name:Breast Cancer Research
         issn:
            1465-542X
         volumeNumber:13
         type:
            Periodical
            PublicationVolume
      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Yinghui Zhang
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Marja Moerkens
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Sreenivasa Ramaiahgari
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Hans de Bont
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Leo Price
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:John Meerman
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:Bob van de Water
            affiliation:
                  name:Leiden University
                  address:
                     name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:1
["Periodical","PublicationVolume"]:
      name:Breast Cancer Research
      issn:
         1465-542X
      volumeNumber:13
Organization:
      name:BioMed Central
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
      name:Leiden University
      address:
         name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Yinghui Zhang
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      name:Marja Moerkens
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      name:Sreenivasa Ramaiahgari
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      name:Hans de Bont
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      name:Leo Price
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      name:John Meerman
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Bob van de Water
      affiliation:
            name:Leiden University
            address:
               name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
      name:Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands

External Links {🔗}(168)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

4.49s.

LINK . SPRINGER . COM {}