Featured Publications
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1RThe Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family
Riese D, van Raaij T, Plowman G, Andrews G, Stern D. The Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family. Molecular And Cellular Biology 1995, 15: 5770-5776. PMID: 7565730, PMCID: PMC230829, DOI: 10.1128/mcb.15.10.5770.Peer-Reviewed Original ResearchConceptsReceptor familyEpidermal growth factor receptor tyrosine kinase familyErbB family receptorsErbB receptor familyReceptor tyrosine kinase familyReceptor tyrosine phosphorylationPeptide agonistsFamily receptorsTyrosine kinase familyHuman cancersReceptor interactionEpidermal growth factor homology domainsCell linesCell survivalReceptorsNeuregulinCellular responsesTyrosine phosphorylationAntiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.
Bangalore L, Tanner AJ, Laudano AP, Stern DF. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 11637-11641. PMID: 1280833, PMCID: PMC50608, DOI: 10.1073/pnas.89.23.11637.Peer-Reviewed Original ResearchEGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions.
Stern DF, Kamps MP. EGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. The EMBO Journal 1988, 7: 995-1001. PMID: 3261240, PMCID: PMC454426, DOI: 10.1002/j.1460-2075.1988.tb02906.x.Peer-Reviewed Original ResearchConceptsEGF-stimulated tyrosine phosphorylationTyrosine phosphorylationEGF receptorKinase activityReceptor-like proteinEGF receptor kinaseIntrinsic kinase activityRat-1 cellsTyrosine kinase activityEpidermal growth factor receptorReceptor kinaseGrowth factor receptorIncubation of cellsPhosphorylationEGFNeu/Factor receptorReceptor interactionSimilar kineticsGrowth factorP185ProteinP185neuReceptorsCellsp185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity.
Stern DF, Heffernan PA, Weinberg RA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Molecular And Cellular Biology 1986, 6: 1729-1740. PMID: 2878363, PMCID: PMC367701, DOI: 10.1128/mcb.6.5.1729.Peer-Reviewed Original ResearchConceptsTyrosine kinase activityEGF receptorGrowth factor receptorProto-oncogeneKinase activityNeu proto-oncogeneC-erbB geneFactor receptorPresence of tunicamycinDistinct electrophoretic mobilitiesEpidermal growth factor receptorNormal culture conditionsMajor structural alterationsTyrosine phosphorylationGene productsNeu oncogeneNormal homologsOncogeneCell linesElectrophoretic mobilityCulture conditionsGrowth factorP185ProteinReceptors
2013
EGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis
Breindel JL, Haskins JW, Cowell EP, Zhao M, Nguyen DX, Stern DF. EGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis. Cancer Research 2013, 73: 5053-5065. PMID: 23794705, PMCID: PMC3745527, DOI: 10.1158/0008-5472.can-12-3775.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaMitogen-activated protein kinaseBrain metastasesEGFR-METMET activationMutant EGFRCell lung carcinomaEffect of MetSMET kinase inhibitorEGF receptorErbB family membersMET amplificationLung carcinomaDrug treatmentTherapeutic targetEGFRMet levelsDrug resistanceCell subpopulationsCarcinoma invasionKinase inhibitorsMET phosphorylationProtein levelsMetSContinued investigation
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
2009
Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells
Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, DiGiovanna MP, Stern DF. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. British Journal Of Cancer 2009, 100: 941-949. PMID: 19240716, PMCID: PMC2661782, DOI: 10.1038/sj.bjc.6604937.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEGFR/HER2 inhibitorsNSCLC cell linesDual EGFR/HER2 inhibitorsGrowth factor receptorMET inhibitorsHER2 inhibitorsUse of EGFREGFR tyrosine kinase inhibitorsCell lung cancer cellsFactor receptorMajority of patientsTreatment of NSCLCCell lung carcinomaTyrosine kinase inhibitorsPotential therapeutic advantagesSubset of tumorsLung cancer cellsCell linesCurrent clinical useReceptor TKTumor cell growthHepatocyte growth factor receptorMaximal growth inhibitionImportant molecular target
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
2005
Relationship of Epidermal Growth Factor Receptor Expression to ErbB-2 Signaling Activity and Prognosis in Breast Cancer Patients
DiGiovanna MP, Stern DF, Edgerton SM, Whalen SG, Moore D, Thor AD. Relationship of Epidermal Growth Factor Receptor Expression to ErbB-2 Signaling Activity and Prognosis in Breast Cancer Patients. Journal Of Clinical Oncology 2005, 23: 1152-1160. PMID: 15718311, DOI: 10.1200/jco.2005.09.055.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor expressionGrowth factor receptor expressionBreast cancer patientsBreast cancerHuman breast cancerFactor receptor expressionErbB-2Cancer patientsReceptor expressionEGFR expressionEarly-stage breast cancerAdverse prognostic valueErbB-2 phosphorylationFirst clinical evidenceInvasive breast cancerPrognosis of patientsPercent of tumorsParaffin tumor sectionsErbB-2 activationErbB-2 overexpressionLigand-dependent mechanismTreatment of tumorsClinical evidencePrognostic valueShorter survival
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-ActivatorsTransgenesErbBs in mammary development
Stern DF. ErbBs in mammary development. Experimental Cell Research 2003, 284: 89-98. PMID: 12648468, DOI: 10.1016/s0014-4827(02)00103-9.Peer-Reviewed Original ResearchConceptsMammary developmentHuman mammary carcinomaCancer therapyHER2/neuNormal mammary developmentEpidermal growth factor receptorGrowth factor receptorMammary carcinomaBreast cancerErbB2/HER2/NeuRational targetReceptor tyrosine kinasesFactor receptorReceptorsErbB familyTherapyTyrosine kinaseFrequent selectionErbBCarcinomaEtiologyCancerMiceNeu
2000
Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases
Stern D. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Research 2000, 2: 176. PMID: 11250707, PMCID: PMC138772, DOI: 10.1186/bcr51.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkersBreast NeoplasmsEpidermal Growth FactorErbB ReceptorsFemaleGene AmplificationGene Expression Regulation, DevelopmentalGene Expression Regulation, NeoplasticGenes, erbBHumansProtein-Tyrosine KinasesReceptor, ErbB-2Signal TransductionTranscriptional ActivationTransforming Growth FactorsTrastuzumabConceptsBreast cancerErbB family receptor tyrosine kinasesReceptor tyrosine kinasesHER2/neuTyrosine kinaseEpidermal growth factor receptorGrowth factor receptorClinical trialsSteroid receptorsTherapeutic antibodiesErbB-2Factor receptorReceptorsCancerPhysiological regulatorSignificant subsetFamily membersKinaseOptimal useNeuHormoneTrialsAntibodiesHerceptin
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
Active signaling by Neu in transgenic mice
DiGiovanna MP, Lerman MA, Coffey RJ, Muller WJ, Cardiff RD, Stern DF. Active signaling by Neu in transgenic mice. Oncogene 1998, 17: 1877-1884. PMID: 9778054, DOI: 10.1038/sj.onc.1202091.Peer-Reviewed Original ResearchConceptsEndogenous epidermal growth factor receptorTransgenic micePhosphorylation state-specific antibodiesMammary tumorsRole of NeuEpidermal growth factor receptorMammary-specific promotersSignal transductionNeu transgenic miceGrowth factor receptorExpression of neuHuman breast cancerNeu activationFactor receptorNeu/Expression levelsMammary neoplasiaMammary lesionsBreast cancerTumor progressionNeuTumorsMiceMonoclonal antibodiesSpecific antibodiesActivation 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 pattern