Featured Publications
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Haskins JW, Zhang S, Means RE, Kelleher JK, Cline GW, Canfrán-Duque A, Suárez Y, Stern DF. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science Signaling 2015, 8: ra111. PMID: 26535009, PMCID: PMC4666504, DOI: 10.1126/scisignal.aac5124.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNeuregulin-1Proto-Oncogene Proteins c-aktReceptor, ErbB-4Receptors, LDLSterol Regulatory Element Binding Protein 2TOR Serine-Threonine KinasesConceptsIntracellular domainEGFR family membersLow-density lipoprotein uptakeCholesterol biosynthesisSREBP target genesRapamycin complex 1ErbB4 intracellular domainSite-1 proteaseCholesterol biosynthesis genesSoluble intracellular domainCholesterol biosynthetic pathwayActivation of ErbB4Mammary epithelial cellsInhibition of AktSterol regulatory elementBiosynthesis genesLipoprotein uptakeRegulatory elementsBiosynthetic pathwayTarget genesDevelopmental processesMetabolic remodelingMature formNeuregulin-1Cellular membranes
2014
Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration
Haskins JW, Nguyen DX, Stern DF. Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration. Science Signaling 2014, 7: ra116. PMID: 25492965, PMCID: PMC4648367, DOI: 10.1126/scisignal.2005770.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCell MovementConnective Tissue Growth FactorErlotinib HydrochlorideFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHippo Signaling PathwayHumansLapatinibMechanotransduction, CellularNeuregulin-1Nuclear ProteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptor, ErbB-4Transcription FactorsConceptsIntracellular domainHippo pathway target genesHippo tumor suppressor pathwayCell migrationTranscriptional coactivator YAPCultured mammary epithelial cellsTumor suppressor pathwayPathway target genesSoluble intracellular domainExpression of genesEpidermal growth factor receptor familyMammary epithelial cellsGrowth factor receptor familyNuclear functionsIntramembrane proteolysisCoactivator YAPFactor receptor familyGrowth factor receptorTarget genesYAP activityNeuregulin-1Receptor tyrosine kinase ErbB4Receptor familyMechanosensory pathwayBreast cancer cell linesConvergent and Divergent Cellular Responses by ErbB4 Isoforms in Mammary Epithelial Cells
Wali VB, Haskins JW, Gilmore-Hebert M, Platt JT, Liu Z, Stern DF. Convergent and Divergent Cellular Responses by ErbB4 Isoforms in Mammary Epithelial Cells. Molecular Cancer Research 2014, 12: 1140-1155. PMID: 24829397, PMCID: PMC4728083, DOI: 10.1158/1541-7786.mcr-13-0637.Peer-Reviewed Original ResearchConceptsYAP/Hippo pathwayIsogenic MCF10A cellsMultiple structural isoformsAlternative mRNA splicingDivergent cellular responsesChIP-seq experimentsProteases/protease inhibitorsErbB4 isoformsMammary epithelial cellsAssociation of ErbB4Hippo pathwayMRNA splicingNovel molecular targetsTranscriptional profilingDivergent functionsTranscription factorsCYT-1Signaling activitiesMevalonate pathwayCellular responsesLuminal breast cancer cell linesDiverse biologic activitiesMCF10A cellsCYT-2Intracellular isoformsOverexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
Wali VB, Gilmore-Hebert M, Mamillapalli R, Haskins JW, Kurppa KJ, Elenius K, Booth CJ, Stern DF. Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis. Breast Cancer Research 2014, 16: 501. PMID: 25516216, PMCID: PMC4303208, DOI: 10.1186/s13058-014-0501-z.Peer-Reviewed Original ResearchConceptsTerminal end budsBreast cancerRole of ErbB4Transgenic miceCYT-2 isoformsMammary glandKi-67-positive cellsNeoplastic mammary lesionsIsoform-specific rolesBetter therapeutic strategiesMammary gland morphologyEpidermal growth factor receptorMammary terminal end budsMammary ductal morphogenesisErbB4 CYT-2Mammary gland developmentTumor suppressor roleGrowth factor receptorPotential oncogenic functionEarly pregnancyCarcinogenic changesNovel oncogenic propertiesMammary lesionsWhole mount analysisErbB4 expression
2010
Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways
Gilmore-Hebert M, Ramabhadran R, Stern DF. Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways. Molecular Cancer Research 2010, 8: 1388-1398. PMID: 20858735, PMCID: PMC3901583, DOI: 10.1158/1541-7786.mcr-10-0042.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChlorocebus aethiopsCOS CellsDNA DamageDown-RegulationErbB ReceptorsGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsProtein BindingReceptor, ErbB-4Repressor ProteinsSignal TransductionSilencer Elements, TranscriptionalSubstrate SpecificityTripartite Motif-Containing Protein 28ConceptsIntracellular domainKinase activityDNA damage response pathwayDamage response pathwayDNA damage responseErbB4 intracellular domainGrowth factor signalingHigh kinase activitySoluble intracellular domainExpression of genesReceptor tyrosine kinasesSuppression of MDM2Candidate interactorsDamage responseResponse pathwaysFactor signalingPlasma membraneMultiple isoformsErbB4 kinase activityTyrosine kinaseDNA damageRole of ErbB4Protein 1KAP1Conjoint regulation
2006
Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4
Jackson-Fisher AJ, Bellinger G, Shum E, Duong JK, Perkins AS, Gassmann M, Muller W, Kent Lloyd KC, Stern DF. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene 2006, 25: 5664-5672. PMID: 16652155, DOI: 10.1038/sj.onc.1209574.Peer-Reviewed Original ResearchConceptsClinical studiesMammary tumorsMammary glandSimilar latency periodHistology of tumorsLoss of ERBB4Epidermal growth factor receptorTumor suppressorGrowth factor receptorLung metastasesBreast cancerErbb4 allelesMMTV-NeuLatency periodNull miceTumorsReceptor tyrosine kinasesFactor receptorErbB4ErbB familyCancerMiceTyrosine kinaseTissue culture analysisGland
2003
Gene expression profiling of ErbB receptor and ligand-dependent transcription
Amin DN, Perkins AS, Stern DF. Gene expression profiling of ErbB receptor and ligand-dependent transcription. Oncogene 2003, 23: 1428-1438. PMID: 14973552, DOI: 10.1038/sj.onc.1207257.Peer-Reviewed Original ResearchConceptsGene expression profilingExpression profilingInfluences gene transcriptionLigand-dependent transcriptionLigand-independent activationTranscriptional targetsGene transcriptionBreast cancerGene expressionMolecular mechanismsSame cell lineReceptor homodimersOligonucleotide arraysBreast cancer cellsUnidentified targetsErbB receptorsOverexpression of ErbB2GenesCancer cellsCell linesTranscriptionErbB4 receptorsErbB2ErbBClinical outcomesNeural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality
Tidcombe H, Jackson-Fisher A, Mathers K, Stern DF, Gassmann M, Golding JP. Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 8281-8286. PMID: 12824469, PMCID: PMC166220, DOI: 10.1073/pnas.1436402100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell MovementCentral Nervous SystemCerebellumCranial NervesDNA, ComplementaryDNA-Binding ProteinsEmbryonic and Fetal DevelopmentErbB ReceptorsFemaleFetal HeartInterneuronsLactationMaleMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMilk ProteinsMorphogenesisMyosinsNeural CrestNeuromuscular JunctionOrgan SpecificityPhosphorylationPhrenic NervePregnancyPromoter Regions, GeneticProtein Processing, Post-TranslationalReceptor, ErbB-4STAT5 Transcription FactorTrans-ActivatorsTransgenes
1999
Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis
Russell K, Stern D, Polverini P, Bender J. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. American Journal Of Physiology 1999, 277: h2205-h2211. PMID: 10600838, DOI: 10.1152/ajpheart.1999.277.6.h2205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCorneaEndothelial Growth FactorsEndothelium, VascularErbB ReceptorsHumansLymphokinesMiceNeovascularization, PhysiologicNeuregulinsRatsReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4ThrombinUmbilical VeinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsHuman umbilical vein endothelial cellsVascular endotheliumErbB receptorsReceptor tyrosine phosphorylationStimulation of HUVECsRapid calcium fluxReceptor family membersEndothelial cell growth factorTransmembrane tyrosine kinase receptorVascular endothelial cell growth factorEndothelial cell signalingReceptor-ligand interactionsTyrosine kinase receptorsEpidermal growth factor receptorVascular endothelial growthCell growth factorUmbilical vein endothelial cellsCell signalingGrowth factor receptorTyrosine phosphorylationVivo angiogenic responseExpression patternsGrowth regulationVein endothelial cellsIntracellular signalingErbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation
Jones F, Welte T, Fu X, Stern D. Erbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation. Journal Of Cell Biology 1999, 147: 77-88. PMID: 10508857, PMCID: PMC2164978, DOI: 10.1083/jcb.147.1.77.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusDNA-Binding ProteinsErbB ReceptorsFemaleGene Expression Regulation, DevelopmentalHumansLactationMammary Glands, AnimalMiceMice, TransgenicMilk ProteinsPhosphorylationPrecipitin TestsPregnancyReceptor, ErbB-4RNA, MessengerSequence DeletionSignal TransductionSrc Homology DomainsSTAT5 Transcription FactorTrans-ActivatorsTransgenesConceptsFunction of ErbB4Dominant-negative alleleMammary glandAlpha-lactalbumin mRNAEpidermal growth factor receptor familyBeta-casein mRNAGrowth factor receptor familyNormal mouse mammary glandMouse mammary glandSH2 domainFactor receptor familyTerminal differentiationProtein mRNAReceptor familyLobuloalveolar developmentAcidic protein mRNASitu hybridizationMammary developmentPhosphorylationErbB4MRNALobuloalveoliUnique responseExpressionImportant role
1998
Activation of ErbB4 by the Bifunctional Epidermal Growth Factor Family Hormone Epiregulin Is Regulated by ErbB2*
Riese D, Komurasaki T, Plowman G, Stern D. Activation of ErbB4 by the Bifunctional Epidermal Growth Factor Family Hormone Epiregulin Is Regulated by ErbB2*. Journal Of Biological Chemistry 1998, 273: 11288-11294. PMID: 9556621, DOI: 10.1074/jbc.273.18.11288.Peer-Reviewed Original Research
1997
Ligands for ErbB-family receptors encoded by a neuregulin-like gene
Chang H, Riese II D, Gilbert W, Stern D, McMahan UJ. Ligands for ErbB-family receptors encoded by a neuregulin-like gene. Nature 1997, 387: 509-512. PMID: 9168114, DOI: 10.1038/387509a0.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsCell LineCerebellumCHO CellsCloning, MolecularCricetinaeErbB ReceptorsGlycoproteinsIn Situ HybridizationLigandsMolecular Sequence DataNeuregulinsPhosphorylationPolymerase Chain ReactionProto-Oncogene ProteinsRatsReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4Recombinant ProteinsTissue DistributionTyrosine
1996
The Epidermal Growth Factor Receptor Couples Transforming Growth Factor-α, Heparin-binding Epidermal Growth Factor-like Factor, and Amphiregulin to Neu, ErbB-3, and ErbB-4*
Riese D, Kim E, Elenius K, Buckley S, Klagsbrun M, Plowman G, Stern D. The Epidermal Growth Factor Receptor Couples Transforming Growth Factor-α, Heparin-binding Epidermal Growth Factor-like Factor, and Amphiregulin to Neu, ErbB-3, and ErbB-4*. Journal Of Biological Chemistry 1996, 271: 20047-20052. PMID: 8702723, DOI: 10.1074/jbc.271.33.20047.Peer-Reviewed Original ResearchMeSH KeywordsAmphiregulinAnimalsCell DivisionCell LineCell SurvivalEGF Family of ProteinsEpidermal Growth FactorErbB ReceptorsGlycoproteinsGrowth SubstancesHeparin-binding EGF-like Growth FactorIntercellular Signaling Peptides and ProteinsInterleukin-3MicePhosphorylationPhosphotyrosineProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4Recombinant ProteinsSignal TransductionTransforming Growth Factor alphaConceptsHeparin-binding EGF-like growth factorErbB family receptorsPhysiologic responsesReceptor tyrosine phosphorylationFamily receptorsGrowth factorEpidermal growth factor (EGF) familyBa/F3 cell lineEpidermal growth factor-like factorsCell linesEGF-like growth factorGrowth factor familyTGF-alphaReceptor couplingReceptors coupleHuman malignanciesAmphiregulinTyrosine phosphorylationEGF familyErbB-3ErbB-4ReceptorsStimulationEGFSimilar patternType 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors.
Bacus SS, Chin D, Yarden Y, Zelnick CR, Stern DF. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. American Journal Of Pathology 1996, 148: 549-58. PMID: 8579117, PMCID: PMC1861670.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsErbB ReceptorsFemaleFrozen SectionsGenes, erbB-2HumansImmunohistochemistryPhosphorylationPhosphotyrosinePrognosisProto-Oncogene MasReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Receptor, ErbB-4Receptors, EstrogenReceptors, ProgesteroneReceptors, SteroidRetrospective StudiesConceptsMammary carcinomaReceptor tyrosine kinasesType 1 receptor tyrosine kinasesMammary carcinoma patientsType 1 receptorExpression of neuAnti-neu antibodyEpidermal growth factor receptorGrowth factor receptorTyrosine kinaseCarcinoma patientsPrognostic factorsPoor prognosisClinical evaluationTherapeutic strategiesCarcinomaHER-4Frozen sectionsSteroid receptorsNeu/ErbBNeuFactor receptorReceptorsDifferent biological activitiesTyrosine phosphorylationBetacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta.
Riese DJ, Bermingham Y, van Raaij TM, Buckley S, Plowman GD, Stern DF. Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. Oncogene 1996, 12: 345-53. PMID: 8570211.Peer-Reviewed Original Research