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Suppression of progesterone receptor signaling by heavy metals promotes tamoxifen resistance and metastasis or ER+ breast cancer
Organization NORTHWESTERN UNIVERSITYLocation CHICAGO, UNITED STATESPosted 24 Jun 2024Deadline 27 May 2025 ⚠️
NIHUS FederalResearch GrantFY2025Active OxygenAddressAdjuvantAdjuvant TherapyAffectAir PollutionAlanineAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsAntioxidantsArsenicArsenitesAutomobile DrivingBiosensorBreast CancerBreast Cancer CellBreast Cancer PatientBreast NeoplasmsBreast Tumor PatientBreast TumorsCancer DrugCell BodyCell Communication and SignalingCell NucleusCell SignalingCellsChemoresistanceChronicClinicalCommunitiesCorpus Luteum HormoneDelta4-pregnene-3,20-dioneDiagnosisDiseaseDisorderDoseDown-RegulationEcological impactEnvironmental ExposureEnvironmental HealthEnvironmental Health ScienceEnvironmental ImpactEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEstrogen ReceptorsEvolutionExposure toExposure to Pb2+FDA approvedGene ExpressionGenesGeneticGoalsHealthHeavy MetalsHeterograftHeterologous TransplantationIndividuals from minorityIndividuals of minorityInternationalIntracellular Communication and SignalingLeadLead levelsLinkLow incomeMaintenanceMalignant Breast NeoplasmMalignant CellMammary CancerMammary NeoplasmsMetalsMetastasisMetastasis InductionMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMetastatic/RecurrentMinorityMinority GroupsMinority PeopleMinority PopulationMinority individualMitochondriaModelingMolecularMolecular FingerprintingMolecular ProfilingMorbidityMorbidity - disease rateNeoplasm MetastasisNeoplastic Disease Chemotherapeutic AgentsNuclearNucleusOrganellesOrganoidsOxidasesOxidation-ReductionOxygen RadicalsPR PositiveParticulatePatientsPb 2+Pb elementPb exposedPb exposurePb levelsPb2+Pb2+ ExposurePb2+ exposedPhenotypePollutionPregn-4-ene-3,20-dionePregnenedionePro-OxidantsProductionProgesteroneProgesterone ReceptorsProgestin ReceptorsPrognosisRNA SeqRNA sequencingRNAseqReactive Oxygen SpeciesReceptor SignalingRecommendationRedoxRefractoryRefractory DiseaseResistanceRiskSERMsSecondary NeoplasmSecondary TumorSelective Estrogen Receptor ModulatorsSignal TransductionSignal Transduction SystemsSignalingSiteSpecific qualifier valueSpecifiedSystemTamoxifenTestingTherapeuticTherapeutic ProgesteroneTreatment EffectivenessTreatment EfficacyTumor CellTumor Cell NucleiTumor-Specific Treatment AgentsWater SupplyWorld HealthWorld Health OrganizationXenograftXenograft procedureXenotransplantationadjuvant treatmentanti-cancer drugarsenicsauthoritybiological sensorbiological signal transductionbreast tumor cellcancer cellcancer metastasiscell transformationchemoresistantchemotherapychemotherapy resistancechemotherapy resistantcostdrivingenvironmental health disparityepigeneticallyexposed to leadexposure to Pbexposure to leadfemale treatmentgene networkheavy metal Pbheavy metal leadin vivoindividuals with breast cancerintervention designintervention efficacyintra-vital microscopyintravital microscopylead exposedlead exposurelead ionlead levellevel of leadmalignant breast tumormammary tumormitochondrialmitochondrial dysfunctionmolecular profilemolecular signaturemortalitymouse modelmurine modelneoplastic cellnoveloxidation reduction reactionpatients with breast cancerperson with breast cancerpharmacologicpollutantpreventpreventingprogesterone receptor positiveprognosticresistantresponse to therapyresponse to treatmentsocio-economicsocio-economicallysocioeconomicallysocioeconomicstherapeutic efficacytherapeutic responsetherapy designtherapy efficacytherapy responsetranscriptome sequencingtranscriptomic sequencingtranscriptomicstransformed cellstreat femalestreat womentreatment among femalestreatment among womentreatment designtreatment in femalestreatment in womentreatment responsetreatment responsivenesstreatment strategytumortumor cell metastasistumor xenograftwomen's treatmentxeno-transplantxeno-transplantation
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Description preview
SUMMARY
The central concept in this project is that exposure of existing estrogen receptor (ER) and
progesterone (PR) positive (ER+/PR+) breast tumors to heavy metal pollutants promotes the
emergence of tumor cells that lack PR expression and function. While ER+/PR+ breast cancer
have excellent prognosis and respond well to treatments, ER+/PR- do…
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