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 ResearchAnimalsCalciumCell DeathFemaleLactationLysosomesMammary Glands, AnimalMilkSTAT3 Transcription Factor
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 ResearchMeSH KeywordsAnimalsBreast NeoplasmsFemaleHumansLactationMammary Glands, AnimalMammary Neoplasms, AnimalMiceParathyroid Hormone-Related ProteinSTAT5 Transcription FactorConceptsOverexpression 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
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
Adipocyte 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
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 ResearchMeSH KeywordsAdult Stem CellsAnimalsEmbryonic Stem CellsFemaleMammary Glands, AnimalMiceMultipotent Stem CellsConceptsAdult 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.BooksMeSH KeywordsAnimalsFemaleHumansMammary Glands, AnimalMammary Glands, HumanMesodermParathyroid Hormone-Related ProteinConceptsParathyroid 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 calcium
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 markersOverexpression
2011
Parathyroid Hormone-Related Protein Is Not Required for Normal Ductal or Alveolar Development in the Post-Natal Mammary Gland
Boras-Granic K, VanHouten J, Hiremath M, Wysolmerski J. Parathyroid Hormone-Related Protein Is Not Required for Normal Ductal or Alveolar Development in the Post-Natal Mammary Gland. PLOS ONE 2011, 6: e27278. PMID: 22087279, PMCID: PMC3210770, DOI: 10.1371/journal.pone.0027278.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene ExpressionLactationMammary Glands, AnimalMiceMice, TransgenicParathyroid Hormone-Related ProteinPregnancyTissue DistributionConceptsMammary glandPTHrP expressionAlveolar developmentMyoepithelial cellsMaternal calcium homeostasisOverexpression of PTHrPRole of PTHrPExpression of PTHrPEmbryonic mammary budPTHrP deficiencyMouse mammary glandParathyroid hormoneTransgenic miceDuctal developmentCalcium homeostasisAlveolar cellsPTHrPPubertal developmentMMTV-CrePost-natal mammary glandMammary developmentMammary budPostnatal mammary glandCre transgenePTHrP gene
2010
PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer
VanHouten J, Sullivan C, Bazinet C, Ryoo T, Camp R, Rimm DL, Chung G, Wysolmerski J. PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 11405-11410. PMID: 20534448, PMCID: PMC2895115, DOI: 10.1073/pnas.0911186107.Peer-Reviewed Original ResearchConceptsPMCA2 expressionBreast cancerT47D breast cancer cellsIntracellular calcium levelsBreast cancer progressionBreast cancer cellsEpithelial cell apoptosisPoor outcomeIntracellular calciumCalcium levelsMammary gland involutionCancer progressionCell apoptosisCancer cellsMammary involutionApoptosisGland involutionCancerMammary epithelial cell apoptosisOutcomesPMCA2Triggers apoptosisApical surfaceExpressionOverexpressionMolecular Mechanisms Guiding Embryonic Mammary Gland Development
Cowin P, Wysolmerski J. Molecular Mechanisms Guiding Embryonic Mammary Gland Development. Cold Spring Harbor Perspectives In Biology 2010, 2: a003251. PMID: 20484386, PMCID: PMC2869520, DOI: 10.1101/cshperspect.a003251.BooksMeSH KeywordsAnimalsCell LineageFemaleGene Expression Regulation, DevelopmentalMammary Glands, AnimalConceptsMammary glandMammary gland developmentBreast cancerEmbryonic mammary developmentBreast developmentEmbryonic mammary gland developmentMammary developmentRegulation of morphogenesisGland developmentMolecular pathwaysPregnancySubsequent developmentDuct systemSexual maturationMolecular mechanismsGlandPotential relevanceSurface ectodermEpidermal appendagesPathophysiologyCancerCharacterization of the Six1 homeobox gene in normal mammary gland morphogenesis
Coletta RD, McCoy EL, Burns V, Kawakami K, McManaman JL, Wysolmerski JJ, Ford HL. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC Developmental Biology 2010, 10: 4. PMID: 20074369, PMCID: PMC2823684, DOI: 10.1186/1471-213x-10-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsFemaleHomeodomain ProteinsHumansLactationMammary Glands, AnimalMiceMice, Inbred C57BLPregnancyTrans-ActivatorsTranscription FactorsConceptsNormal mammary gland developmentAdult mammary glandMammary gland developmentMammary glandMammary developmentBreast cancerMouse modelBreast tumorigenesisEmbryonic mammary glandPostnatal mammary developmentRag1-/- miceNormal mammary gland morphogenesisGland developmentTransgenic mouse modelBreast cancer initiationViable therapeutic targetIndependent mouse modelsAdult mouse mammary glandAnti-cancer therapyMammary stem cellsFamily membersMouse mammary glandUnwanted side effectsRole of Six1Invasive carcinoma
2009
Analysis of gene expression in PTHrP−/− mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis
Hens J, Dann P, Hiremath M, Pan T, Chodosh L, Wysolmerski J. Analysis of gene expression in PTHrP−/− mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis. Developmental Dynamics 2009, 238: 2713-2724. PMID: 19795511, PMCID: PMC2862621, DOI: 10.1002/dvdy.22097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 4Cells, CulturedDipeptidesDown-RegulationGene Expression Regulation, DevelopmentalHydroxamic AcidsIntercellular Signaling Peptides and ProteinsKeratinsMammary Glands, AnimalMatrix Metalloproteinase 2Matrix Metalloproteinase InhibitorsMesodermMiceMice, KnockoutMorphogenesisOligonucleotide Array Sequence AnalysisParathyroid Hormone-Related ProteinProtease InhibitorsSignal TransductionTranscription FactorsUp-RegulationConceptsGene expressionMammary budMammary mesenchymeDuctal outgrowthMesenchymal cellsEmbryonic mammary developmentMMP2 gene expressionEmbryonic mammary budFunctional roleGenesDuctal morphogenesisBud culturesMammary developmentBudsPTHrP effectsBMPMesenchymeExpressionMMP2 activityMMP2OutgrowthVentral skinCellsMorphogenesisBMP4
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