2024
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution
Jeong J, Lee J, Talaia G, Kim W, Song J, Hong J, Yoo K, Gonzalez D, Athonvarangkul D, Shin J, Dann P, Haberman A, Kim L, Ferguson S, Choi J, Wysolmerski J. Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution. Cellular And Molecular Life Sciences 2024, 81: 29. PMID: 38212474, PMCID: PMC10784359, DOI: 10.1007/s00018-023-05044-8.Peer-Reviewed Original Research
2022
PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development
Grinman DY, Boras-Granic K, Takyar FM, Dann P, Hens JR, Marmol C, Lee J, Choi J, Chodosh LA, Sola MEG, Wysolmerski JJ. PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development. Breast Cancer Research 2022, 24: 30. PMID: 35440032, PMCID: PMC9020078, DOI: 10.1186/s13058-022-01523-1.Peer-Reviewed Original ResearchConceptsOverexpression of PTHrPSecretory differentiationEpithelial cellsPTHrP overexpressionTumor latencyBreast cancerMammary epithelial cellsType 1 PTH/PTHrP receptorMMTV-PyMT breast cancer modelPTH/PTHrP receptorMMTV-PyMT miceMammary tumor developmentBreast cancer riskBreast cancer biologyExpression of PTHrPHormone-related proteinHuman breast cancerBreast cancer modelE74-like factor 5Normal mammary epithelial cellsBreast cancer progressionMouse mammary tumorsExpression of markersAlveolar epithelial cellsLuminal epithelial cells
2021
MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells
Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ, Yan Q, Liu Y, Choi J, Wysolmerski J. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Reports 2021, 37: 110160. PMID: 34965434, PMCID: PMC8762588, DOI: 10.1016/j.celrep.2021.110160.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBreast NeoplasmsCell ProliferationCytoskeletal ProteinsDrug Resistance, NeoplasmEndocytosisFemaleHumansMembrane MicrodomainsMyelin and Lymphocyte-Associated Proteolipid ProteinsPhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2Sodium-Hydrogen ExchangersTrastuzumabTumor Cells, CulturedConceptsLipid raft formationBreast cancer cellsLipid raftsLipid raft resident proteinsCancer cellsRaft formationRaft-resident proteinsProximity ligation assayProtein complexesMembrane protrusionsProtein interactionsPlasma membraneLigation assayMAL2Membrane stabilityStructural organizationPotential therapeutic targetPhysical interactionMembrane retentionProteinRaftsTherapeutic targetCellsIntracellular calcium concentrationLow intracellular calcium concentration
2019
Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Lotinun S, Ishihara Y, Nagano K, Kiviranta R, Carpentier VT, Neff L, Parkman V, Ide N, Hu D, Dann P, Brooks D, Bouxsein ML, Wysolmerski J, Gori F, Baron R. Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression. Journal Of Clinical Investigation 2019, 129: 3058-3071. PMID: 31112135, PMCID: PMC6668688, DOI: 10.1172/jci122936.Peer-Reviewed Original ResearchConceptsLactation-induced bone lossParathyroid hormoneBone lossBone resorptionCathepsin KMilk calcium levelsParathyroid hormone suppressionSerum parathyroid hormoneRegulation of PTHOsteoclastic bone resorptionTrabecular bone volumeOsteocyte lacunar areaHormone suppressionHigh calcium demandOsteoclast numberCortical thicknessEffect of lactationCalcium levelsNormal rangeBone volumeCalcium demandExact mechanismLacunar areaResorptionSufficient calciumNHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland
Jeong J, Kim W, Hens J, Dann P, Schedin P, Friedman PA, Wysolmerski JJ. NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland. Endocrinology 2019, 160: 1797-1810. PMID: 31087002, PMCID: PMC6619491, DOI: 10.1210/en.2019-00230.Peer-Reviewed Original ResearchConceptsPlasma membrane calcium ATPase 2Mammary epithelial cellsSpecialized plasma membrane domainsMammary epithelial cell deathLuminal epithelial cellsCell deathPremature mammary gland involutionBreast cancer cellsApical-basal polarityEpithelial cellsPlasma membrane domainsApical membraneSecretory luminal epithelial cellsExchanger regulatory factor 1Cell death pathwaysNHERF1 expressionMammary gland involutionCancer cellsRegulatory factor 1Sodium-hydrogen exchanger regulatory factor-1Lactating Mammary GlandNormal mammary epithelial cellsMembrane localizationEpithelial cell deathMembrane domains
2018
Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells
Jeong J, Choi J, Kim W, Dann P, Takyar F, Gefter JV, Friedman PA, Wysolmerski J. Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells. Journal Of Biological Chemistry 2018, 294: 887-901. PMID: 30463939, PMCID: PMC6341383, DOI: 10.1074/jbc.ra118.004143.Peer-Reviewed Original ResearchConceptsBreast cancer cellsBreast cancerCancer cellsHER2-positive breast cancer cell linesHER2-positive breast cancer cellsInvasive breast cancerDegradation of HER2Breast cancer cell linesHuman breast cancerNormal mammary epithelial cellsInhibition of EzrinHER2 tyrosine kinaseErbB family membersPMCA2 levelsCancer cell linesDuctal carcinomaHER2 expressionHER2 levelsMammary epithelial cellsHER2Human patientsPharmacologic inhibitionActive HER2Ezrin expressionGenetic knockdownAdipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nature Communications 2018, 9: 3592. PMID: 30181538, PMCID: PMC6123393, DOI: 10.1038/s41467-018-05911-0.Peer-Reviewed Original ResearchConceptsMouse mammary glandMilk-producing epithelial cellsTissue-specific rolesMammary glandAdipose growthLipid dynamicsGenetic tracingPhysiological examplesFunctional implicationsCellular mechanismsAdipocyte hypertrophyMature adipocytesEssential roleVivo analysisTissue functionMammary epitheliumAdipocytesEpithelial cellsAdipocyte precursorsSubsequent involutionMilk lipidsPrimary mechanismMechanismLipidomicsMilk fat production
2017
The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2
Jeong J, VanHouten JN, Kim W, Dann P, Sullivan C, Choi J, Sneddon WB, Friedman PA, Wysolmerski JJ. The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2. Journal Of Biological Chemistry 2017, 292: 6555-6568. PMID: 28235801, PMCID: PMC5399107, DOI: 10.1074/jbc.m116.770883.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsApoptosisBreast NeoplasmsCalciumCell Line, TumorCell MembraneCell ProliferationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansMiceMicroscopy, FluorescencePhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2RNA, MessengerSignal TransductionSodium-Hydrogen ExchangersConceptsBreast cancerHER2-positive breast cancerHER2-positive statusInvasive breast cancerHuman ductal carcinomaDegradation of HER2Normal mammary epithelial cellsMalignant breast cellsBreast cancer cellsErbB2/HER2Tyrosine kinase HER2Sodium-hydrogen exchanger regulatory factor-1Ductal carcinomaHER2 expressionExchanger regulatory factor 1Mammary epithelial cellsHER2Regulatory factor 1NHERF1 expressionBreast cellsEpithelial cellsCancerCancer cellsFactor 1PMCA2
2016
Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein
Kim W, Takyar FM, Swan K, Jeong J, VanHouten J, Sullivan C, Dann P, Yu H, Fiaschi-Taesch N, Chang W, Wysolmerski J. Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein. Cancer Research 2016, 76: 5348-5360. PMID: 27450451, PMCID: PMC5026591, DOI: 10.1158/0008-5472.can-15-2614.Peer-Reviewed Original ResearchConceptsMMTV-PyMT miceBreast cancer cellsCaSR activationBone metastasesBreast cancerInhibited tumor cell proliferationOsteolytic bone metastasesCancer cellsHuman breast cancer cell linesCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinTransgenic mouse modelBreast cancer cell linesMMTV-PyMT transgenic mouse modelBreast cancer progressionTumor cell proliferationTumor cell growthCancer cell linesPTHrP levelsTissue-specific disruptionHigh extracellular concentrationsPTHrP productionCASR genePTHrP expressionPMCA2 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
2015
OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism
Ardeshirpour L, Dumitru C, Dann P, Sterpka J, VanHouten J, Kim W, Kostenuik P, Wysolmerski J. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism. Endocrinology 2015, 156: 2762-2773. PMID: 25961842, PMCID: PMC4511126, DOI: 10.1210/en.2015-1232.Peer-Reviewed Original ResearchConceptsBone lossOPG treatmentOsteoblast numberActivated B cells ligandLactational bone lossMaternal calcium homeostasisMaternal calcium metabolismMilk calcium levelsRapid bone lossDietary calcium intakeMaternal bone lossBone resorption rateMaternal hypocalcemiaRecombinant OPGCalcium intakeMaternal deathsOsteoprotegerin levelsMaternal skeletonBone turnoverDietary calciumCalcium metabolismOsteoclast numberBone massOsteoclast activityAnabolic response
2014
Deletion of the Nuclear Localization Sequences and C-Terminus of PTHrP Impairs Embryonic Mammary Development but also Inhibits PTHrP Production
Boras-Granic K, Dann P, VanHouten J, Karaplis A, Wysolmerski J. Deletion of the Nuclear Localization Sequences and C-Terminus of PTHrP Impairs Embryonic Mammary Development but also Inhibits PTHrP Production. PLOS ONE 2014, 9: e90418. PMID: 24785493, PMCID: PMC4006745, DOI: 10.1371/journal.pone.0090418.Peer-Reviewed Original ResearchConceptsMammary gland developmentType 1 PTH/PTHrP receptorC-terminusEmbryonic mammary gland developmentPTH/PTHrP receptorGland developmentPTHrP mRNA levelsNuclear localization signalNuclear localization sequenceHormone-related proteinEmbryonic mammary developmentMammary epithelial cellsLocalization signalNuclear functionsPTHrP productionPTHrP receptorAlternative animal modelLocalization sequencePTHR1 geneAnimal modelsEndocrine fashionMutant formsPTHrPDevelopmental defectsMesenchyme differentiationEmbryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland
Boras-Granic K, Dann P, Wysolmerski JJ. Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland. Breast Cancer Research 2014, 16: 487. PMID: 25467960, PMCID: PMC4308878, DOI: 10.1186/s13058-014-0487-6.Peer-Reviewed Original ResearchConceptsAdult mammary glandMammary glandLabel-retaining cellsCell populationsFuture breast cancer riskStem cellsDNA label retentionBreast cancer riskStem cell populationEdU-labeled cellsEmbryonic day 18.5Label retaining cellsAdult mouse mammary glandStem/progenitor cellsMammary stem cellsStem/progenitor cell populationsSecondary mammospheresEmbryonic day 14.5Fetal exposureMouse mammary glandOvarian hormonesQuiescent stem cell populationMulti-potent stem cellsCancer riskBasal markers
2013
Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual
Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual. Endocrinology 2013, 154: 3031-3042. PMID: 23782944, PMCID: PMC3749485, DOI: 10.1210/en.2012-2195.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiological TransportBone DevelopmentBone ResorptionCalciumCrosses, GeneticFemaleGene Expression RegulationLactationLactoglobulinsMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMilkParathyroid HormoneParathyroid Hormone-Related ProteinReceptors, Calcium-SensingRNA, MessengerConceptsRenal calcium excretionCalcium excretionCalcium metabolismBone resorptionCalcium transportMilk calciumMammary glandAccelerated bone resorptionMammary-specific ablationMaternal calcium metabolismDietary calcium intakeCalcium sensing receptorCalcium-sensing receptorSecretion of PTHrPSkeletal calcium storesMilk PTHrPCalcium intakePTH secretionPTHrP secretionMaternal boneBone turnoverBone metabolismOnset of lactationMaternal circulationSystemic calciumParathyroid Hormone-Related Protein Specifies the Mammary Mesenchyme and Regulates Embryonic Mammary Development
Hiremath M, Wysolmerski J. Parathyroid Hormone-Related Protein Specifies the Mammary Mesenchyme and Regulates Embryonic Mammary Development. Journal Of Mammary Gland Biology And Neoplasia 2013, 18: 171-177. PMID: 23640717, PMCID: PMC3696739, DOI: 10.1007/s10911-013-9283-7.BooksConceptsParathyroid hormoneBreast cancerMammary rudimentsMammary budLoss of PTHrPOverexpression of PTHrPRole of PTHrPEffects of PTHrPNovel breast cancer susceptibility lociEpithelial-stromal crosstalkEmbryonic mammary budBreast cancer susceptibility lociEmbryonic mammary developmentMammary gland morphogenesisNipple skinDay 15PTHrP’s rolePTHrPMammary developmentMammary epithelial identityMammary mesenchymeCancer susceptibility lociCancerCritical regulatorHormoneThe calcium-sensing receptor in the breast
VanHouten JN, Wysolmerski JJ. The calcium-sensing receptor in the breast. Best Practice & Research Clinical Endocrinology & Metabolism 2013, 27: 403-414. PMID: 23856268, PMCID: PMC3713417, DOI: 10.1016/j.beem.2013.02.011.BooksConceptsG-protein usageBreast cancer cellsCalcium-sensing receptorCalcium metabolismCancer cellsParathyroid hormone-related protein levelsBreast cellsMaternal calcium metabolismOsteolytic skeletal metastasesSystemic calcium metabolismEpithelial cellsNormal breast epithelial cellsFeed-forward cycleMalignant breast cellsNormal breast cellsBreast epithelial cellsSkeletal metastasesPTHrP productionPTHrP expressionMammary epithelial cellsCaSRCalcium transportProtein levelsTransport of calciumSupply of calciumAttacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy
Espina V, Wysolmerski J, Edmiston K, Liotta LA. Attacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy. Women's Health 2013, 9: 157-170. PMID: 23477322, PMCID: PMC3779365, DOI: 10.2217/whe.13.5.BooksConceptsBreast cancerBreast cancer stem-like cellsCancer stem-like cellsBreast carcinoma cellsStem-like cellsDuctal carcinomaPreinvasive carcinomaPreinvasive neoplasmsClinical trialsIntracellular calciumSevere hypoxicTherapeutic strategiesNeoplastic cellsCarcinoma cellsMetabolic stressCarcinomaTherapyCancerCellsSurvival mechanismAutophagyNeoplasmsTrialsHypoxicOsteocytes remove and replace perilacunar mineral during reproductive cycles
Wysolmerski JJ. Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone 2013, 54: 230-236. PMID: 23352996, PMCID: PMC3624069, DOI: 10.1016/j.bone.2013.01.025.BooksConceptsBone lossLevels of PTHrPNegative calcium balanceLevels of estrogenPrincipal bone-resorbing cellsSkeletal calcium storesBone-resorbing cellsPTHrP levelsBone turnoverBone resorptionBone massMineral metabolismCalcium balanceRole of osteocytesCalcium storesMineral homeostasisOsteocytic osteolysisReproductive cycleOsteocytesSystemic demandsPericanalicular matrixCalciumLactationBone
2012
Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme
Hiremath M, Dann P, Fischer J, Butterworth D, Boras-Granic K, Hens J, Van Houten J, Shi W, Wysolmerski J. Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme. Development 2012, 139: 4239-4249. PMID: 23034629, PMCID: PMC3478689, DOI: 10.1242/dev.080671.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCell DifferentiationFemaleGene Expression Regulation, DevelopmentalKeratinocytesLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMesodermMiceMice, KnockoutParathyroid Hormone-Related ProteinReceptors, Parathyroid HormoneThrombospondinsWnt ProteinsWnt Signaling PathwayConceptsLoss of PTHrPOverexpression of PTHrPHormone-related proteinMammary mesenchymeΒ-cateninEmbryonic mammary mesenchymeWnt pathwayWnt/β-cateninEmbryonic mammary developmentCanonical Wnt pathwayPTHrPMammary developmentMammary budAbnormal differentiationReduced expressionBasal keratinocytesVentral skinReporter activityBud cellsMarkersCanonical WntInappropriate differentiationAbolished expressionMesenchyme markersOverexpressionPTHrP and breast cancer: more than hypercalcemia and bone metastases
Boras-Granic K, Wysolmerski JJ. PTHrP and breast cancer: more than hypercalcemia and bone metastases. Breast Cancer Research 2012, 14: 307. PMID: 22546075, PMCID: PMC3446368, DOI: 10.1186/bcr3129.BooksConceptsBone metastasesBreast cancerMMTV-PyMT miceNormal breast developmentPrimary breast tumorsHormone-related proteinBreast cancer susceptibility genesNew breast cancer susceptibility genesCancer patientsPrimary tumorCancer susceptibility genesClinical investigationBreast developmentBreast tumorsTumor growthPTHrPMetastasisHypercalcemiaTumorsCancerSusceptibility genesFurther researchPatientsMice