Featured Publications
ErbB2 is required for ductal morphogenesis of the mammary gland
Jackson-Fisher AJ, Bellinger G, Ramabhadran R, Morris JK, Lee KF, Stern DF. ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17138-17143. PMID: 15569931, PMCID: PMC535384, DOI: 10.1073/pnas.0407057101.Peer-Reviewed Original ResearchConceptsKinase geneNormal mouse mammary gland developmentReceptor kinase geneMammary budMouse mammary gland developmentReceptor tyrosine kinase geneTyrosine kinase geneMammary gland developmentMammary glandImportant normal functionsFunctions of ErbB2Gland developmentDuctal morphogenesisEpithelial treeLobuloalveolar developmentTerminal end budsLuminal spaceBudsGenesErbB2End budsHuman breast cancerAggressive phenotypeBreast cancerNormal functionActivation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface
Burke C, Stern D. Activation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface. Molecular And Cellular Biology 1998, 18: 5371-5379. PMID: 9710621, PMCID: PMC109122, DOI: 10.1128/mcb.18.9.5371.Peer-Reviewed Original Research3T3 CellsAmino Acid SequenceAmino Acid SubstitutionAnimalsCell LineCell Transformation, NeoplasticCOS CellsCysteineDimerizationDisulfidesDNA PrimersMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPolymerase Chain ReactionProtein Structure, SecondaryRatsReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Recombinant ProteinsSequence AlignmentActivation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor.
DiGiovanna MP, Stern DF. Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor. Cancer Research 1995, 55: 1946-55. PMID: 7728765.Peer-Reviewed Original ResearchConceptsHuman breast tumorsBreast tumorsPrimary human breast tumorsPoor patient prognosisSubset of tumorsEpidermal growth factor receptorGrowth factor receptorPatient prognosisImmunohistochemical stainingNeu/ErbBTumor samplesTumorsMonoclonal antibodiesHuman tumorsFactor receptorRelated receptorsReceptorsP185Polyclonal antibodiesAntibodiesErbBRelated epidermal growth factor receptorSubsetTyrosine phosphoproteinsPrognosisAntiserum 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 Researchp185, 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
2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
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
2008
ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer
Stern DF. ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer. Journal Of Mammary Gland Biology And Neoplasia 2008, 13: 215. PMID: 18454306, PMCID: PMC6590701, DOI: 10.1007/s10911-008-9083-7.Peer-Reviewed Original ResearchConceptsBreast cancerCancer etiologyErbB3/HER3Breast cancer etiologyAdditional therapeutic opportunitiesEpidermal growth factor receptor familyGrowth factor receptor familyAkt-dependent pathwayFactor receptor familyMouse modelERBB2 amplificationNeuregulin-2Neuregulin-1Therapeutic opportunitiesTherapeutic toolMammary developmentRegulation of metabolismCancerReceptor familyAggressive propertiesTherapeutic compoundsErbB2ErbB3Eventual developmentEtiologyDirect resequencing of the complete ERBB2 coding sequence reveals an absence of activating mutations in ERBB2 amplified breast cancer
Zito CI, Riches D, Kolmakova J, Simons J, Egholm M, Stern DF. Direct resequencing of the complete ERBB2 coding sequence reveals an absence of activating mutations in ERBB2 amplified breast cancer. Genes Chromosomes And Cancer 2008, 47: 633-638. PMID: 18418848, PMCID: PMC6668724, DOI: 10.1002/gcc.20566.Peer-Reviewed Original ResearchInfluence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
DiGiovanna MP, Stern DF, Edgerton S, Broadwater G, Dressler LG, Budman DR, Henderson IC, Norton L, Liu ET, Muss HB, Berry DA, Hayes DF, Thor AD. Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B. Journal Of Clinical Oncology 2008, 26: 2364-2372. PMID: 18390970, PMCID: PMC6589994, DOI: 10.1200/jco.2007.13.6580.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicinEnzyme ActivationFemaleFluorouracilGene DosageHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLymphatic MetastasisNeoplasm StagingPhosphorylationReceptor, ErbB-2ConceptsLeukemia Group BAdjuvant cyclophosphamideErbB-2Breast cancerGroup BAnthracycline-based adjuvant chemotherapyNode-positive breast cancerAdverse prognostic factorSpecific chemotherapeutic agentsErbB-2 overexpressionActivation stateTumor tissue sectionsAdjuvant chemotherapyCAF doseCALGB 8541Fluorouracil chemotherapyPrognostic factorsAssessable casesFavorable outcomePatientsChemotherapeutic agentsStage IICancerDoseTissue sections
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 survivalPhosphorylated/Activated HER2 as a Marker of Clinical Resistance to Single Agent Taxane Chemotherapy for Metastatic Breast Cancer
Modi S, DiGiovanna MP, Lu Z, Moskowitz C, Panageas KS, Van Poznak C, Hudis CA, Norton L, Tan L, Stern DF, Carter D, Seidman AD. Phosphorylated/Activated HER2 as a Marker of Clinical Resistance to Single Agent Taxane Chemotherapy for Metastatic Breast Cancer. Cancer Investigation 2005, 23: 483-487. PMID: 16203655, DOI: 10.1080/07357900500201301.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSingle-agent taxane therapyTaxane therapyP-HER2Clinical benefitBreast cancerClinical resistanceSingle-agent taxane chemotherapyUnique predictive informationChi-squared analysisTaxane chemotherapyClinical outcomesClinical progressionTaxane monotherapyHER2 statusClinical trialsPhosphorylated HER2Tumor specimensFunctional assessmentHER2TherapyMonoclonal antibodiesImmunohistochemistrySquared analysisProgression
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 outcomes
2002
Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates.
DiGiovanna MP, Chu P, Davison TL, Howe CL, Carter D, Claus EB, Stern DF. Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates. Cancer Research 2002, 62: 6667-73. PMID: 12438265.Peer-Reviewed Original ResearchConceptsHER-2/neuCases of DCISDuctal carcinomaPrognostic indicatorNeu overexpressionHER-2/neu statusAdverse prognostic indicatorHormone receptor expressionPresence of calcificationIndicator of angiogenesisClinicopathological correlatesNeu levelsTumor sizeNeu expressionInvasive carcinomaHER-2Positivity rateReceptor expressionNeu statusBreast tumorigenesisDCISNeuCarcinomaMonoclonal antibodiesSignificant correlation
2001
Pathobiologic Findings in DCIS of the Breast: Morphologic Features, Angiogenesis, HER-2/neu and Hormone Receptors
Claus E, Chu P, Howe C, Davison T, Stern D, Carter D, DiGiovanna M. Pathobiologic Findings in DCIS of the Breast: Morphologic Features, Angiogenesis, HER-2/neu and Hormone Receptors. Experimental And Molecular Pathology 2001, 70: 303-316. PMID: 11418009, DOI: 10.1006/exmp.2001.2366.Peer-Reviewed Original ResearchConceptsHigh nuclear gradeEstrogen receptorNuclear gradePeriductal fibrosisProgesterone receptorNeu overexpressionComedo histologyPR expressionExpression of ERHER-2/neuAssociated invasive carcinomaCases of DCISHospital-based surveyBiology of DCISPotential clinical implicationsDuctal carcinomaTumor sizePathologic markersInvasive carcinomaNeu expressionBreast carcinomaCase subjectsDCISClinical implicationsMorphologic features
2000
Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): a study of incidence and correlation with outcome in breast cancer.
Thor AD, Liu S, Edgerton S, Moore D, Kasowitz KM, Benz CC, Stern DF, DiGiovanna MP. Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): a study of incidence and correlation with outcome in breast cancer. Journal Of Clinical Oncology 2000, 18: 3230-9. PMID: 10986055, DOI: 10.1200/jco.2000.18.18.3230.Peer-Reviewed Original ResearchConceptsBreast cancerErbB-2 expressionPrognostic valueErbB-2Node-positive breast cancerNode-positive patientsPositive lymph nodesDisease-specific survivalPrimary breast cancerAdditional prognostic valueInvasive breast cancerNode-positive casesBreast cancer patientsSignificant prognostic valueStudy of incidenceArchival breast cancer samplesErbB-2-positive cellsBreast cancer samplesBreast cancer cellsInvasive breast cancer cellsIdentification of casesLymph nodesPatient groupPoor prognosisCancer patientsTyrosine 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 signalingExpression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation
Jones F, Stern D. Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation. Oncogene 1999, 18: 3481-3490. PMID: 10376526, DOI: 10.1038/sj.onc.1202698.Peer-Reviewed Original ResearchConceptsNormal mouse mammary gland developmentDominant-negative alleleMouse mammary gland developmentMammary glandErbB2/HER2/NeuMammary gland developmentMouse mammary glandNegative allelesFunctions of ErbB2ErbB2 signalingGland developmentLobuloalveolar developmentMammary developmentProtein expressionHuman breast cancerErbB2Transgenic miceExpressionPhenotypeLobuloalveoliSignalingOverexpression