Untangling the ErbB signalling network | Nature Reviews Molecular Cell Biology

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c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Yosef-Yarden-Aff1" data-author-popup="auth-Yosef-Yarden-Aff1" data-author-search="Yarden, Yosef">Yosef Yarden</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> & </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Mark_X_-Sliwkowski-Aff2" data-author-popup="auth-Mark_X_-Sliwkowski-Aff2" data-author-search="Sliwkowski, Mark X.">Mark X. Sliwkowski</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> </li></ul> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/nrm" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature Reviews Molecular Cell Biology</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 2</b>, <span class="u-visually-hidden">pages </span>127–137 (<span data-test="article-publication-year">2001</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">31k <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">23 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/35052073/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Key Points" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Key Points</h2><div class="c-article-section__content" id="Abs1-content"> <ul class="u-list-style-bullet"> <li> <p> The four ErbB receptors and their many neuregulins and EGF-like ligands form a layered signalling network. The network structure allows the diversification, tuning and robustness of cell-to-cell signalling. </p> </li> <li> <p> The network evolved from a simple signalling module that controls inductive morphogenesis in invertebrates. In mammals, specific ligands and their respective homo- or heterodimeric ErbB complexes specify different cell lineages. </p> </li> <li> <p> Oncogenic animal viruses harness the network through diverse molecular processes that promote ErbB signalling or prevent it from being switched off. </p> </li> <li> <p> Autocrine loops, mutant ErbB1 molecules and enhanced expression of ErbB receptors are frequently observed in human cancers of epithelial and neuronal origins. Most frequent is overexpression of ErbB2, a ligandless co-receptor that amplifies ErbB signalling. </p> </li> <li> <p> Current attempts to block the network in human disease include small-molecule inhibitors of tyrosine kinases and chaperones, and various gene-therapy strategies. But immunotherapy directed at ErbB2 is already widely used, in combination with chemotherapy, to inhibit metastasizing breast cancers. </p> </li> <li> <p> Future pharmacological advances and deeper understanding of the network will allow selective inhibition or activation of its many routes, with the aim of curing neuronal and skin disorders, as well as cancer.</p> </li> </ul> </div></div></section><section aria-labelledby="Abs2" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs2-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs2">Abstract</h2><div class="c-article-section__content" id="Abs2-content"><p>When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin®), a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. 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data-test="figure" data-container-section="figure" id="figure-2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 2: Crosstalk between the ErbB network and other signalling pathways.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig2_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig2_HTML.gif" alt="" loading="lazy" width="312" height="229"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 3: Signalling by ErbB homodimers in comparison with ErbB2-containing heterodimers. </b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig3_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig3_HTML.gif" alt="" loading="lazy" width="312" height="288"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-4"><figure><figcaption><b id="Fig4" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 4: Therapeutic strategies for blocking the ErbB signalling network.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig4_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2F35052073/MediaObjects/41580_2001_Article_BF35052073_Fig4_HTML.gif" alt="" loading="lazy" width="312" height="273"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-5"><figure><figcaption><b id="Fig5" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 5: Molecular diagnosis of breast cancer.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" 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Sliwkowski</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Yosef-Yarden-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Yosef Yarden</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Yosef%20Yarden" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Yosef%20Yarden" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Yosef%20Yarden%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Mark_X_-Sliwkowski-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Mark X. Sliwkowski</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Mark%20X.%20Sliwkowski" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Mark%20X.%20Sliwkowski" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Mark%20X.%20Sliwkowski%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li></ol></div></div></div></section><section aria-labelledby="appendices"><div class="c-article-section" id="appendices-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="appendices">Related links</h2><div class="c-article-section__content" id="appendices-content"><h3 class="c-article__sub-heading u-visually-hidden" id="App1">Related links</h3><h3 class="c-article__sub-heading" id="Sec6">DATABASE LINKS</h3><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1956"> ErbB1</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=nrg*%20not%20rc3&ORG=Hs"> NRGs</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2065"> ErbB3</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2066"> ErbB4</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2064"> ErbB2</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1950"> EGF</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2069"> epiregulin</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3084"> NRG1β</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=685"> betacellulin</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=pik*&ORG=Hs"> PI(3)K</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=shc1%20or%20%20shc3&ORG=Hs"> Shc</a> </p><p> <a href="">p70S6K</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=prkca%20or%20prkcb%20or%20prkcf%20or%20prkcd%20or%20prkce%20or%20prkch%20or%20prkci%20or%20prkcn%20or%20prkcm%20or%20prkcz&ORG=Hs"> PKC</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=Akt&ORG=Hs"> Akt</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2886"> Grb7</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2353"> <i> fos</i> </a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3725"> <i> jun</i> </a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4609"> <i> myc</i> </a> </p><p> <a href="http://www.ebi.ac.uk/interpro/IEntry?ac=IPR002991"> zinc finger</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6667"> Sp1</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1958"> Egr1</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=gabp*&ORG=Hs"> GABP</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2885"> Grb2</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=PLC*%20%20and%20gamma&ORG=Hs"> phospholipase Cγ</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6714"> Src</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2185"> Pyk2</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=arrb*&ORG=Hs"> arrestin</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3717"> Jak2</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3569"> interleukin-6</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7039"> TGF-α</a> </p><p> <a href="http://sdb.bio.purdue.edu/fly/torstoll/egf-r1.htm"><i> Drosophila</i> EGF receptor</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=15238"> NRG1</a> </p><p> <a href="http://pharminfo.com/drugdb/db_mnuh.html">Herceptin </a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1027"> p27<sup>Kip1</sup></a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5925"> Rb</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=9221"> p130</a> </p><p> <a href="http://clinicaltrials.gov/ct/gui/c/a1r/action/SearchAction/screen/OpeningScreen?JServSessionIdcs_current=o6pg9ef0nn&Term=cetuximab&submit=Search"> C225</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3326"> Hsp90</a> </p><p> <a href="http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=374"> amphiregulin</a> </p><p> <a href="http://flybase.bio.indiana.edu/.bin/fbidq.html?FBgn0003985"> Vein</a> </p><p> <a href="http://flybase.bio.indiana.edu/.bin/fbidq.html?FBgn0001137"> Gurken</a> </p><p> <a href="http://flybase.bio.indiana.edu/.bin/fbidq.html?FBgn0005672"> Spitz</a> </p><p> <a href="http://flybase.bio.indiana.edu/.bin/fbidq.html?FBgn0004569"> Argos</a> </p><h3 class="c-article__sub-heading" id="Sec7">FURTHER INFORMATION</h3><p> <a href="http://www.biomedcomp.com/tgdb.html"> The tumour gene database</a> </p><h3 class="c-article__sub-heading" id="Sec8">ENCYCLOPEDIA OF LIFE SCIENCES</h3><p> <a href="http://www.els.net/els/FDA/default.asp?id=76FEF39E-7ACB-4F3E-BEB5-9F8E84362CF7"><i> Drosophila</i> embryo: dorsal–ventral specification</a> </p></div></div></section><section data-title="Glossary"><div class="c-article-section" id="glossary-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="glossary">Glossary</h2><div class="c-article-section__content" id="glossary-content"><dl class="c-description-list"><dt class="c-description-list__term u-text-bold" id="Glos1">MESENCHYME</dt><dd class="c-description-list__description u-pl-32"> <p>Immature connective tissue that consists of cells embedded in extracellular matrix.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos2">NEUREGULINS</dt><dd class="c-description-list__description u-pl-32"> <p>EGF-like ligands whose primary receptor is ErbB3 and/or ErbB4. Four types of neuregulin are known.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos3">STROMA</dt><dd class="c-description-list__description u-pl-32"> <p>Supporting connective tissue in which a glandular or other epithelium is embedded.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos4">HUMANIZED MONOCLONAL ANTIBODY</dt><dd class="c-description-list__description u-pl-32"> <p>An antibody, usually from a rodent, engineered to contain mainly human sequences. This process reduces the immune response to the antibody in humans.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos5">ADAPTOR PROTEINS</dt><dd class="c-description-list__description u-pl-32"> <p>Proteins that augment cellular responses by recruiting other proteins to a complex. They usually contain several protein–protein interaction domains.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos6">EGF-LIKE DOMAIN</dt><dd class="c-description-list__description u-pl-32"> <p>A motif with <span class="stix">∼</span>50 amino acids, including six cysteine residues and a mainly β-sheet structure, found in all ErbB-binding growth factors and in extracellular matrix proteins.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos7">IMMUNOGLOBULIN-LIKE DOMAIN</dt><dd class="c-description-list__description u-pl-32"> <p>A protein domain composed of two β-pleated sheets held together by a disulphide bond.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos8">METALLOPROTEINASES</dt><dd class="c-description-list__description u-pl-32"> <p>Proteinases that have a metal ion at their active sites.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos9">MESODERM</dt><dd class="c-description-list__description u-pl-32"> <p>The middle germ layer of the developing embryo. It gives rise to the musculoskeletal, vascular and urinogenital systems, and to connective tissue (including that of the dermis).</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos10">ECTODERM</dt><dd class="c-description-list__description u-pl-32"> <p>The outermost germ layer of the developing embryo. It gives rise to the epidermis and the nerves.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos11">AKT PATHWAY</dt><dd class="c-description-list__description u-pl-32"> <p>Akt (or protein kinase B) is a serine/threonine protein kinase activated by the phosphatidylinositol-3-OH kinase pathway that activates survival responses.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos12">STRESS-ACTIVATED PROTEIN KINASES </dt><dd class="c-description-list__description u-pl-32"> <p>Members of the mitogen-activated protein kinase (MAPK) family that respond to stress. They include the Jun amino-terminal kinases (JNKs) and the p38 MAPKs.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos13">UBIQUITIN LIGASES</dt><dd class="c-description-list__description u-pl-32"> <p>Enzymes that catalyse the last stage of ubiquitylation, in which the small protein ubiquitin is transferred from a ubiquitin-conjugating enzyme (UBC or E2) to its target protein. They are also known as E3 enzymes.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos14">GAPS</dt><dd class="c-description-list__description u-pl-32"> <p>Proteins that inactivate small GTP-binding proteins, such as Ras family members, by increasing their rate of GTP hydrolysis.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos15">GLIA</dt><dd class="c-description-list__description u-pl-32"> <p>Supporting cells of the nervous system, including oligodendrocytes and astrocytes in the central nervous system, and Schwann cells in the peripheral nervous system. Glia surround neurons, providing mechanical and physical support, and electrical insulation between neurons.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos16">SCHWANN CELLS</dt><dd class="c-description-list__description u-pl-32"> <p>Cells that produce myelin and ensheath axons in the peripheral nervous system.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos17">TRABECULAE</dt><dd class="c-description-list__description u-pl-32"> <p>Finger-like projections of cardiac muscle cells that form ridges in the ventricular wall.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos18">SYMPATHETIC GANGLIA</dt><dd class="c-description-list__description u-pl-32"> <p>Clusters of sympathetic neurons in which a glandular or other epithelium is embedded.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos19">NEURAL CREST</dt><dd class="c-description-list__description u-pl-32"> <p>A group of embryonic cells that separate from the embryonic neural plate and migrate, giving rise to the spinal and autonomic ganglia, peripheral glia, chromaffin cells, melanocytes and some haematopoietic cells.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos20">CLONAL EXPANSION</dt><dd class="c-description-list__description u-pl-32"> <p>Growth of a population of cells from a single precursor cell.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos21">CARCINOMA</dt><dd class="c-description-list__description u-pl-32"> <p>A malignant tumour of epithelial origin.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos22">PROGNOSIS</dt><dd class="c-description-list__description u-pl-32"> <p>The likely outcome or course of a disease.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos23">ANDROGEN-DEPENDENT PROSTATE CANCER </dt><dd class="c-description-list__description u-pl-32"> <p>An early form of prostate cancer that is responsive to androgens and anti-androgen therapy.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos24">AUTOCRINE</dt><dd class="c-description-list__description u-pl-32"> <p>Activation of cellular receptors by ligands produced by the same cell.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos25">GENE AMPLIFICATION</dt><dd class="c-description-list__description u-pl-32"> <p>A differential increase in a specific portion of the genome. Amplification is associated with neoplastic transformation and acquisition of drug resistance.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos26">DUCTAL BREAST CANCER</dt><dd class="c-description-list__description u-pl-32"> <p>Cancer arising from the lining of the milk ducts, as opposed to the lobules of the breast (lobular breast cancer).</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos27">ANEUPLOIDY</dt><dd class="c-description-list__description u-pl-32"> <p>An abnormal number of chromosomes caused by their inaccurate segregation during cell division.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos28">FLUORESCENCE <i>IN SITU</i> HYBRIDIZATION </dt><dd class="c-description-list__description u-pl-32"> <p>Visualizing a genetic marker on a chromosome by using a fluorescently labelled polynucleotide probe that hybridizes to a gene on a chromosome during metaphase.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos29">FARNESYLTRANSFERASE INHIBITORS</dt><dd class="c-description-list__description u-pl-32"> <p>Inhibitors that block the activity of Ras by preventing the addition of a farnesyl group that targets it to the plasma membrane.</p> </dd><dt class="c-description-list__term u-text-bold" id="Glos30">TYRPHOSTINS</dt><dd class="c-description-list__description u-pl-32"> <p>A type of tyrosine kinase inhibitor.</p> </dd></dl></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"><p class="c-article-rights"><a data-track="click" data-track-action="view rights and permissions" data-track-label="link" href="https://s100.copyright.com/AppDispatchServlet?title=Untangling%20the%20ErbB%20signalling%20network&author=Yosef%20Yarden%20et%20al&contentID=10.1038%2F35052073&copyright=Springer%20Nature%20Limited&publication=1471-0072&publicationDate=2001-02-01&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions</a></p></div></div></section><section aria-labelledby="article-info" data-title="About this article"><div class="c-article-section" id="article-info-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="article-info">About this article</h2><div class="c-article-section__content" id="article-info-content"><div class="c-bibliographic-information"><div class="c-bibliographic-information__column"><h3 class="c-article__sub-heading" id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Yarden, Y., Sliwkowski, M. 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