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
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
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 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 markersOverexpressionDemonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation
Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jähn K, Kato S, Wysolmerski J, Bonewald LF. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. Journal Of Bone And Mineral Research 2012, 27: 1018-1029. PMID: 22308018, PMCID: PMC3770147, DOI: 10.1002/jbmr.1567.Peer-Reviewed Original Research
2011
Site‐specific changes in bone microarchitecture, mineralization, and stiffness during lactation and after weaning in mice
Liu XS, Ardeshirpour L, VanHouten JN, Shane E, Wysolmerski JJ. Site‐specific changes in bone microarchitecture, mineralization, and stiffness during lactation and after weaning in mice. Journal Of Bone And Mineral Research 2011, 27: 865-875. PMID: 22189918, DOI: 10.1002/jbmr.1503.Peer-Reviewed Original ResearchConceptsWhole bone stiffnessNulliparous miceBone microarchitectureTissue mineralizationBone mineral density BMDIndividual trabecula segmentationDramatic bone lossBone mineral densityBone stiffnessRecovered miceBone lossMineral densityPup weaningEffect of lactationMouse modelSkeletal sitesBone quantityClinical observationsMicro-finite element analysisBone qualitySite-specific changesSkeletal changesDigital topological analysisMiceCortical structuresParathyroid 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 ResearchConceptsMammary 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 geneSkeletal recovery after weaning does not require PTHrP*
Kirby BJ, Ardeshirpour L, Woodrow JP, Wysolmerski JJ, Sims NA, Karaplis AC, Kovacs CS. Skeletal recovery after weaning does not require PTHrP*. Journal Of Bone And Mineral Research 2011, 26: 1242-1251. PMID: 21308774, PMCID: PMC3179289, DOI: 10.1002/jbmr.339.Peer-Reviewed Original ResearchConceptsBone mineral contentParathyroid hormoneBone massSerum calciumLumbar spine bone mineral contentTrabecular bone mineral contentParathyroid hormone-related proteinSpine bone mineral contentBone formationNormal serum calciumLow bone massAdult bone massPTHrP mRNA expressionWild-type miceHormone-related proteinEnd of lactationType 1 collagenUrine calciumSkeletal recoveryPTHrP mRNANull miceMRNA expressionFull recoveryMiceConditional knockout
2010
Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton
Ardeshirpour L, Brian S, Dann P, VanHouten J, Wysolmerski J. Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton. Endocrinology 2010, 151: 5591-5601. PMID: 21047946, PMCID: PMC2999486, DOI: 10.1210/en.2010-0566.Peer-Reviewed Original ResearchConceptsBone mineral densityBone lossEstrogen deficiencyMineral densityInfusion of PTHrPReversible bone lossLevels of estrogenCombination of OVXLeuprolide treatmentCentral hypogonadismGnRH agonistMaternal skeletonBone turnoverOsmotic minipumpsOsteoclast numberBone metabolismBone resorptionSurgical ovariectomyNulliparous micePTHrPOVXInfusionEstrogenLeuprolideModest declinePMCA2 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 surfaceExpressionOverexpressionCharacterization 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 ResearchConceptsNormal 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
The calcium-sensing receptor couples to Gαs and regulates PTHrP and ACTH secretion in pituitary cells
Mamillapalli R, Wysolmerski J. The calcium-sensing receptor couples to Gαs and regulates PTHrP and ACTH secretion in pituitary cells. Journal Of Endocrinology 2009, 204: 287-297. PMID: 20032198, PMCID: PMC3777408, DOI: 10.1677/joe-09-0183.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsACTH secretionCAMP productionProtein-coupled receptorsDifferent G proteinsCaR couplesAtT-20 cellsHormone secretionExtracellular calciumSystemic calcium homeostasisBiological functionsG proteinsBreast cancer cellsCell typesCalcium-sensing receptorCell growthReceptors coupleMalignant breast cellsCancer cellsKidney cellsBreast cellsCAR activationPituitary corticotrophsCalcium homeostasisAnterior pituitaryAnalysis 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