Featured Publications
Activation 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 phosphoproteinsPrognosis
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
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 isoformsSignificance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway
Colavito SA, Zou MR, Yan Q, Nguyen DX, Stern DF. Significance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Research 2014, 16: 444. PMID: 25252859, PMCID: PMC4303124, DOI: 10.1186/s13058-014-0444-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationClaudinsEpithelial-Mesenchymal TransitionFemaleGene ExpressionHeterocyclic Compounds, 2-RingHumansMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsNF-kappa BPromoter Regions, GeneticProtein BindingReceptor Cross-TalkRNA, MessengerSignal TransductionThiazolesTranscription FactorsZinc Finger Protein GLI1ConceptsGlioma-associated oncogene homolog 1Claudin-low cell linesBreast cancer stem cellsCancer stem cellsOncogene homolog 1Gli1 expressionBreast cancerClaudin-low breast cancer subtypeMetastatic breast cancer stem cellsNFκB pathwayCell linesClaudin-low breast cancerActivated B cells (NF-κB) pathwayClaudin-low subtypeHomolog 1Breast cancer subtypesMarkers of EMTB-cell pathwayNFκB subunit p65Stem cellsMesenchymal-like characteristicsPoor prognosisTreatment optionsOrthotopic xenograftsAggressive type
2013
Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method
Bai Y, Cheng H, Bordeaux J, Neumeister V, Kumar S, Rimm DL, Stern DF. Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method. PLOS ONE 2013, 8: e79901. PMID: 24278211, PMCID: PMC3836903, DOI: 10.1371/journal.pone.0079901.Peer-Reviewed Original ResearchConceptsCore needle biopsyBreast cancer casesResection specimensCancer casesHER2/neu overexpressionPrediction of responsePre-analytic variablesNeu overexpressionTumor resectionNeedle biopsyBreast cancerHER2 immunoreactivityRetrospective collectionHER2Drug trastuzumabClinical implicationsHER2 proteinQuantitative immunofluorescenceResectionPHER2Good responseFurther studiesBiopsyTrastuzumabImmunoreactivity
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
Neuregulin-regulated gene expression in mammary carcinoma cells
Amin DN, Tuck D, Stern DF. Neuregulin-regulated gene expression in mammary carcinoma cells. Experimental Cell Research 2005, 309: 12-23. PMID: 15963498, DOI: 10.1016/j.yexcr.2005.04.034.Peer-Reviewed Original ResearchConceptsDual-specificity phosphatase 5FBJ murine osteosarcoma viral oncogene homolog BMyelocytomatosis viral oncogeneSerum response factorDehydrogenase/reductaseMammary epithelial cell lineEarly growth response 1Gene expression profilingCell linesTransient receptor potential channel 1Transcription factor 3Growth factorForkhead box C1Phosphatase 5Cullin-1Epithelial cell lineExpression profilingGene expressionMolecular mechanismsMolecular eventsViral oncogenesBreast tumor initiationResponse 1Platelet/endothelial cell adhesion molecule-1ErbB familyRelationship 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
1997
Cripto Enhances the Tyrosine Phosphorylation of Shc and Activates Mitogen-activated Protein Kinase (MAPK) in Mammary Epithelial Cells*
Kannan S, De Santis M, Lohmeyer M, David J, Smith G, Hynes N, Seno M, Brandt R, Bianco C, Persico G, Kenney N, Normanno N, Martinez-Lacaci I, Ciardiello F, Stern D, Gullick W, Salomon D. Cripto Enhances the Tyrosine Phosphorylation of Shc and Activates Mitogen-activated Protein Kinase (MAPK) in Mammary Epithelial Cells*. Journal Of Biological Chemistry 1997, 272: 3330-3335. PMID: 9013573, DOI: 10.1074/jbc.272.6.3330.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveBreast NeoplasmsCalcium-Calmodulin-Dependent Protein KinasesEnzyme ActivationEpidermal Growth FactorEpitheliumFemaleGPI-Linked ProteinsGrowth SubstancesHumansIntercellular Signaling Peptides and ProteinsMammary Glands, AnimalMembrane GlycoproteinsMiceMitogen-Activated Protein Kinase 1Neoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesSrc Homology DomainsTumor Cells, CulturedTyrosineConceptsTyrosine phosphorylationHC-11 cellsMammary epithelial cellsErb BCripto-1Ras/Raf/MEK/MAPK pathwayTyrosine kinaseRaf/MEK/MAPK pathwayMitogen-activated protein kinase activityMEK/MAPK pathwayHC-11 mouse mammary epithelial cellsEpithelial cellsMouse mammary epithelial cellsProtein kinase activityTyrosine-phosphorylated ShcReceptor tyrosine kinasesDifferent human breast cancer cell linesSKBR-3 breast cancer cellsType 1 receptor tyrosine kinasesEGF-like growth factorHuman breast cancer cell linesEpidermal growth factor (EGF) familyBreast cancer cell linesActivates MitogenGrowth factor family
1996
Functional assay for HER-2/neu demonstrates active signalling in a minority of HER-2/neu-overexpressing invasive human breast tumours
DiGiovanna M, Carter D, Flynn S, Stern D. Functional assay for HER-2/neu demonstrates active signalling in a minority of HER-2/neu-overexpressing invasive human breast tumours. British Journal Of Cancer 1996, 74: 802-806. PMID: 8795585, PMCID: PMC2074709, DOI: 10.1038/bjc.1996.439.Peer-Reviewed Original ResearchConceptsHER-2/neuPrognostic indicatorBreast carcinomaInvasive breast carcinomaHER-2/ neuHuman breast tumorsFunctional assaysHuman breast carcinomaClinicopathological characteristicsPoor prognosisInvasive human breast tumoursLarge seriesBreast tumorsNeuMonoclonal antibodiesCarcinomaTumorsAntibodiesDifferent reportsOverexpressionReportAssaysPrognosis