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
The butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation
Jeong J, Kadegowda AKG, Meyer TJ, Jenkins LM, Dinan JC, Wysolmerski JJ, Weigert R, Mather IH. The butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation. FASEB BioAdvances 2021, 3: 971-997. PMID: 34938960, PMCID: PMC8664049, DOI: 10.1096/fba.2021-00059.Peer-Reviewed Original ResearchWild-type cellsAcute phase response genesCell death pathwaysMouse linesFos/JunMutant mouse linesMammary epitheliumMammary epithelial cellsButyrophilin 1A1Secretion complexDeath routeProteomic analysisNuclear DNADeath pathwaysResponse genesOptimal milk productionExpression of cyclinsCaspase-8Upregulation of Ki67Cell deathMembrane receptorsType cellsLipid dropletsRedox enzymesLysosomal lysis
2020
Calcium metabolism and breast cancer: Echoes of lactation?
Grinman D, Athonvarungkul D, Wysolmerski J, Jeong J. Calcium metabolism and breast cancer: Echoes of lactation? Current Opinion In Endocrine And Metabolic Research 2020, 15: 63-70. PMID: 33299957, PMCID: PMC7720883, DOI: 10.1016/j.coemr.2020.11.006.BooksBreast cancerSystemic calcium homeostasisBreast cancer cellsMaternal calciumMammary epithelial cellsCalcium metabolismBone metabolismSystemic metabolismIntracellular calciumMalignant behaviorCalcium homeostasisCalcium receptorCalcium secretionSeries of adaptationsUptake of calciumMammary glandEpithelial cellsCalcium transportCancer cellsCell proliferationExtracellular fluidCancerCalciumMetabolismLactation
2019
NHERF1 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 knockdown
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 in Breast Physiology and Cancer
Kim W, Wysolmerski JJ. Calcium-Sensing Receptor in Breast Physiology and Cancer. Frontiers In Physiology 2016, 7: 440. PMID: 27746743, PMCID: PMC5043011, DOI: 10.3389/fphys.2016.00440.BooksBreast cancer cellsPTHrP productionCancer cellsInhibits cell deathMammary epithelial cellsEpithelial cellsG-protein usageBreast cancer cell proliferationElevated extracellular calcium levelsOsteolytic bone metastasesNormal breast epithelial cellsNuclear pathwaysCalcium sensing receptorCalcium-sensing receptorBreast epithelial cellsBreast cancer progressionCancer cell proliferationExtracellular calcium levelsNormal breast cellsProtein secretionCell deathCancer progressionBone metastasesPTHrP secretionCellular proliferation
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 differentiation
2013
The 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 calcium
2008
Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*
Mamillapalli R, VanHouten J, Zawalich W, Wysolmerski J. Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*. Journal Of Biological Chemistry 2008, 283: 24435-24447. PMID: 18621740, PMCID: PMC2528989, DOI: 10.1074/jbc.m801738200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone NeoplasmsBreast NeoplasmsCell Line, TumorCyclic AMPCyclic AMP-Dependent Protein KinasesFemaleGTP-Binding Protein alpha SubunitsHumansHypercalcemiaLactationMammary Glands, AnimalMammary Neoplasms, AnimalMAP Kinase Signaling SystemMiceNeoplasm MetastasisNeoplasm ProteinsParathyroid Hormone-Related ProteinPregnancyReceptors, Calcium-SensingType C PhospholipasesConceptsG-protein usagePTHrP productionMammary epithelial cellsBreast cancer cellsBreast cellsMCF-7 cellsParathyroid hormone-related protein secretionParathyroid hormone-related proteinParathyroid hormone secretionCancer cellsMCF-7 human breast cancer cellsCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinNormal mammary epithelial cellsRegulation of calciumMalignant breast cellsNormal breast cellsG protein-coupled receptorsG protein couplingBone metastasesPTHrP secretionHormone secretionBone metabolismBreast cancer
2007
Transcellular Calcium Transport in Mammary Epithelial Cells
VanHouten JN, Wysolmerski JJ. Transcellular Calcium Transport in Mammary Epithelial Cells. Journal Of Mammary Gland Biology And Neoplasia 2007, 12: 223-235. PMID: 17999165, DOI: 10.1007/s10911-007-9057-1.BooksThe Calcium-Sensing Receptor Regulates Plasma Membrane Calcium Adenosine Triphosphatase Isoform 2 Activity in Mammary Epithelial Cells: A Mechanism for Calcium-Regulated Calcium Transport into Milk
VanHouten JN, Neville MC, Wysolmerski JJ. The Calcium-Sensing Receptor Regulates Plasma Membrane Calcium Adenosine Triphosphatase Isoform 2 Activity in Mammary Epithelial Cells: A Mechanism for Calcium-Regulated Calcium Transport into Milk. Endocrinology 2007, 148: 5943-5954. PMID: 17823248, PMCID: PMC7108505, DOI: 10.1210/en.2007-0850.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportBlotting, WesternCalciumCells, CulturedEpithelial CellsFemaleFluorescent Antibody TechniqueGadoliniumIsoenzymesLactationMammary Glands, AnimalMiceMice, Inbred BALB CMicroscopy, ImmunoelectronMilkMilk ProteinsMutationOligonucleotide Array Sequence AnalysisPlasma Membrane Calcium-Transporting ATPasesReceptors, Calcium-SensingReverse Transcriptase Polymerase Chain ReactionConceptsPlasma membrane calcium ATPase isoform 2Mammary epithelial cellsMouse mammary epithelial cellsEpH4 mouse mammary epithelial cellsEpithelial cellsGenome-wide screening strategyApical plasma membraneATPase activityPotential downstream targetsATPase isoform 2Mouse mammary glandPlasma membrane preparationsDeafwaddler miceTransepithelial calcium transportPlasma membraneDownstream targetsGene knockdownPMCA2 activityCalcium transportIsoform 2Calcium-dependent ATPase activityCell membraneCultured primaryCalcium-sensing receptorPMCA2 expressionBMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction
Hens JR, Dann P, Zhang JP, Harris S, Robinson GW, Wysolmerski J. BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Development 2007, 134: 1221-1230. PMID: 17301089, DOI: 10.1242/dev.000182.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 4Bone Morphogenetic Protein Receptors, Type IBone Morphogenetic ProteinsDNA-Binding ProteinsEmbryo, MammalianGene Expression Regulation, DevelopmentalHair FollicleHomeodomain ProteinsMammary Glands, AnimalMesodermMiceMice, Mutant StrainsParathyroid Hormone-Related ProteinRNA, MessengerSignal TransductionUp-RegulationConceptsMammary mesenchymeBMP signalingMammary budMesenchymal cellsMammary epithelial cell fateEpithelial cell fateParathyroid hormone-related proteinHair follicle inductionEmbryonic mammary developmentMammary bud formationHormone-related proteinHair follicle formationMammary epithelial cellsMsx2 gene expressionCell fateEmbryonic epidermisMsx2 geneMsx2 expressionMammary placodesMouse embryosGene expressionVentral epidermisDuctal developmentBMP4Bud formation
2005
The calcium-sensing receptor regulates PTHrP production and calcium transport in the lactating mammary gland
Ardeshirpour L, Dann P, Pollak M, Wysolmerski J, VanHouten J. The calcium-sensing receptor regulates PTHrP production and calcium transport in the lactating mammary gland. Bone 2005, 38: 787-793. PMID: 16377269, DOI: 10.1016/j.bone.2005.11.009.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorPTHrP productionMammary epithelial cellsMammary glandCalcium transportEpithelial cellsCalcium homeostasisParathyroid hormone-related proteinParathyroid hormone secretionProduction of PTHrPHormone-related proteinSystemic calcium homeostasisExtracellular calcium ionsTransepithelial calcium transportG protein-coupled receptorsHormone secretionParathyroid glandsBone massCalcium handlingRenal tubulesTransient lossGlandGenetic confirmationReceptorsSecretion
2004
The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport
VanHouten J, Dann P, McGeoch G, Brown EM, Krapcho K, Neville M, Wysolmerski JJ. The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport. Journal Of Clinical Investigation 2004, 113: 598-608. PMID: 14966569, PMCID: PMC338258, DOI: 10.1172/jci18776.Peer-Reviewed Original ResearchConceptsParathyroid hormone-related protein productionCalcium-sensing receptorMammary epithelial cellsEpithelial cellsCalcium transportMilk calcium contentExtracellular calcium concentrationSecretion of calciumTranscellular calcium transportPTHrP secretionPTHrP productionExtracellular calciumTransfer of calciumCalcium contentMammary glandCalcium concentrationProtein concentrationAvailability of calciumHomeostatic systemConcentration of calciumMilk osmolalitySecretionCalciumReceptorsThree-dimensional culture system
2003
Mammary-specific deletion of parathyroid hormone–related protein preserves bone mass during lactation
VanHouten JN, Dann P, Stewart AF, Watson CJ, Pollak M, Karaplis AC, Wysolmerski JJ. Mammary-specific deletion of parathyroid hormone–related protein preserves bone mass during lactation. Journal Of Clinical Investigation 2003, 112: 1429-1436. PMID: 14597768, PMCID: PMC228471, DOI: 10.1172/jci19504.Peer-Reviewed Original ResearchConceptsBone lossBone turnoverMammary epithelial cellsParathyroid hormone-related proteinMammary glandMammary-specific deletionPTHrP-knockout miceRapid bone lossEpithelial cellsDihydroxy vitamin DNegative calcium balanceHormone-related proteinPreserves bone massAbsence of PTHrPExpression of CreUrinary cAMPVitamin DBone resorptionLate pregnancyBone massPTHrP mRNACalcium balanceKnockout micePTHrP proteinMammary development
2001
Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development
Foley J, Dann P, Hong J, Cosgrove J, Dreyer B, Rimm D, Dunbar M, Philbrick W, Wysolmerski J. Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development 2001, 128: 513-525. PMID: 11171335, DOI: 10.1242/dev.128.4.513.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCell DifferentiationCell LineageCytoskeletal ProteinsDNA-Binding ProteinsEpidermal CellsEpidermisEpithelial CellsFemaleGene Expression Regulation, DevelopmentalHistocytochemistryLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMiceMice, KnockoutMice, TransgenicModels, BiologicalNipplesParathyroid Hormone-Related ProteinProteinsReceptor, Parathyroid Hormone, Type 1Receptors, Parathyroid HormoneSignal TransductionTrans-ActivatorsTranscription FactorsTransgenesConceptsPTH/PTHrP receptorCell fateHormone-related proteinMammary epithelial cell fateMammary mesenchymeCell fate decisionsEpithelial cell fatePTHrP receptorEmbryonic mammary glandMesenchymal cellsType I PTH/PTHrP receptorEmbryonic mammary developmentMammary epithelial cellsParathyroid hormone-related proteinEpithelial cellsEpithelial fateEpidermal fateFate decisionsEpithelial morphogenesisAbsence of PTHrPMesenchymal expressionVentral epidermisProper developmentSkin differentiationCombination of loss
1999
Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development
Dunbar M, Dann P, Robinson G, Hennighausen L, Zhang J, Wysolmerski J. Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development. Development 1999, 126: 3485-3493. PMID: 10409496, DOI: 10.1242/dev.126.16.3485.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedApoptosisEpithelial CellsFemaleGene Expression Regulation, DevelopmentalHeterozygoteMaleMammary Glands, AnimalMesodermMiceMice, KnockoutParathyroid Hormone-Related ProteinProteinsReceptor, Parathyroid Hormone, Type 1Receptors, AndrogenReceptors, Parathyroid HormoneSex CharacteristicsTenascinConceptsAndrogen receptorMammary mesenchymeMammary budPTH/PTHrP receptorParathyroid hormone-related proteinHormone-related proteinEpithelial budsAR expressionPTHrP expressionMale micePTHrP receptorEmbryonic mammary developmentMammary epithelial cellsEpithelial-mesenchymal signalingMammary developmentTransgenic overexpressionMammary glandBasal epidermisEpithelial cellsC expressionTenascin CVentral dermisReceptorsAndrogensPTHrP
1998
Stromal Cells Are Critical Targets in the Regulation of Mammary Ductal Morphogenesis by Parathyroid Hormone-Related Protein
Dunbar M, Young P, Zhang J, McCaughern-Carucci J, Lanske B, Orloff J, Karaplis A, Cunha G, Wysolmerski J. Stromal Cells Are Critical Targets in the Regulation of Mammary Ductal Morphogenesis by Parathyroid Hormone-Related Protein. Developmental Biology 1998, 203: 75-89. PMID: 9806774, DOI: 10.1006/dbio.1998.9029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveCyclic AMPEmbryonic and Fetal DevelopmentEpitheliumFemaleGene Expression Regulation, DevelopmentalIn Situ HybridizationMammary Glands, AnimalMesodermMiceMice, Inbred StrainsMorphogenesisParathyroid Hormone-Related ProteinProteinsReceptors, Parathyroid HormoneRNA, MessengerStromal CellsConceptsPTH/PTHrP receptorPTHrP receptorStromal cellsMammary epithelial cell morphogenesisMammary developmentEpithelial cell morphogenesisMammary glandAmino-terminal PTHrPEpithelial cellsHormone-related proteinMammary ductal morphogenesisMammary epithelial cellsCritical targetMammary stromal cellsDuctal branching morphogenesisDevelopmental regulatory moleculeStromal cell functionMurine mammary glandCell morphogenesisMammary morphogenesisHumoral hypercalcemiaParathyroid hormoneTumor productsRegulatory moleculesMammary mesenchymeRescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development
Wysolmerski J, Philbrick W, Dunbar M, Lanske B, Kronenberg H, Karaplis A, Broadus A. Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development. Development 1998, 125: 1285-1294. PMID: 9477327, DOI: 10.1242/dev.125.7.1285.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedGene DeletionGene Expression Regulation, DevelopmentalGene Transfer TechniquesImmunohistochemistryIn Situ HybridizationMammary Glands, AnimalMiceMice, KnockoutMorphogenesisParathyroid Hormone-Related ProteinPhenotypeProteinsReceptors, Parathyroid HormoneRNA, MessengerConceptsHormone-related proteinMammary epithelial cellsMammary gland developmentEpithelial cellsPTH/PTHrP receptor expressionPTH/PTHrP receptorParathyroid hormone-related proteinMammary glandPTH/PTHrP receptor geneAmino-terminal PTHrPMammary duct systemPTHrP-knockout miceMammary mesenchymeOverexpression of PTHrPGland developmentPTHrP receptor expressionProtein knockout miceAbsence of PTHrPSitu hybridization histochemistryAbility of PTHrPTransgenic expressionEpithelial-mesenchymal communicationNeonatal deathHumoral hypercalcemiaEarly pregnancy