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
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 calcium
2017
HER2 signaling regulates HER2 localization and membrane retention
Jeong J, Kim W, Kim LK, VanHouten J, Wysolmerski JJ. HER2 signaling regulates HER2 localization and membrane retention. PLOS ONE 2017, 12: e0174849. PMID: 28369073, PMCID: PMC5378417, DOI: 10.1371/journal.pone.0174849.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisBreast NeoplasmsCalciumCell Line, TumorCell MembraneCell ProliferationErbB ReceptorsGene Knockdown TechniquesHumansIntracellular SpaceLapatinibPlasma Membrane Calcium-Transporting ATPasesQuinazolinesReceptor, ErbB-2Receptor, ErbB-3RNA, Small InterferingUbiquitinationConceptsMembrane protrusionsCell surfaceSpecific plasma membrane domainsPlasma membrane domainsReceptor tyrosine kinasesMembrane domainsErbB family membersErbB3/HER3Tyrosine kinaseGenetic knockdownHER2 ubiquitinationHER2/HER3PMCA2 expressionPharmacologic inhibitionUbiquitinationERBB2 geneHsp90HER2/EGFRCalcium pumpMembrane retentionInternalizationHuman breast cancerFamily membersHER3ExpressionThe 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
PMCA2 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
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
2011
Skeletal 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
Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation
Wysolmerski JJ. Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation. Annals Of The New York Academy Of Sciences 2010, 1192: 161-169. PMID: 20392232, PMCID: PMC3777748, DOI: 10.1111/j.1749-6632.2009.05249.x.Books
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 expression
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 confirmationReceptorsSecretionContinuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)2Vitamin D
Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia‐Ocaña A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP Infusion Causes Suppression of Bone Formation and Discordant Effects on 1,25(OH)2Vitamin D. Journal Of Bone And Mineral Research 2005, 20: 1792-1803. PMID: 16160737, DOI: 10.1359/jbmr.050602.Peer-Reviewed Original ResearchConceptsContinuous infusionVitamin DBone formationPhosphorus handlingRenal calciumIGF-1Anabolic skeletal responseDoses of PTHVitamin D homeostasisVitamin D metabolismPlasma IGF-1Vitamin D productionVitamin D synthesisOsteoblastic bone formationHealthy young adultsRenal PTH receptorsContinuous PTHCalcemic responseD homeostasisPrimary hyperparathyroidismHumoral hypercalcemiaSerum calciumD metabolismBone turnoverBone resorptionHypercalcemia in Breast Cancer: An Echo of Bone Mobilization During Lactation?
DeMauro S, Wysolmerski J. Hypercalcemia in Breast Cancer: An Echo of Bone Mobilization During Lactation? Journal Of Mammary Gland Biology And Neoplasia 2005, 10: 157-167. PMID: 16025222, DOI: 10.1007/s10911-005-5398-9.BooksConceptsBreast cancer patientsBone resorptionCancer patientsBreast cancerParathyroid hormone-related proteinPathophysiology of hypercalcemiaMultiple skeletal metastasesPathological bone resorptionHormone-related proteinActivation of osteoclastsSecretion of cytokinesClass of drugsSkeletal calcium storesNormal breast cellsFrequent complicationSkeletal metastasesSignificant morbidityCalcium metabolismCurrent therapiesHypercalcemiaNew therapiesCalcium levelsOsteoclast differentiationCalcium storesPatients
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 developmentLow Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice
VanHouten JN, Wysolmerski JJ. Low Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice. Endocrinology 2003, 144: 5521-5529. PMID: 14500568, DOI: 10.1210/en.2003-0892.Peer-Reviewed Original ResearchConceptsBone lossBone mineral densityBone resorptionMineral densityDual-energy X-ray absorptiometryBone resorption markersX-ray absorptiometryRegulation of calciumAge-matched virginsPamidronate treatmentPTHrP levelsResorption markersLow estrogenEstrogen deficiencyBone turnoverEstrogen levelsPregnant miceBone metabolismBone massPeptide levelsSkeletal metabolismTotal bodyBone volumeCalcium homeostasisBiochemical markersA Syndrome of Hypocalciuric Hypercalcemia Caused by Autoantibodies Directed at the Calcium-Sensing Receptor
Kifor O, Moore FD, Delaney M, Garber J, Hendy GN, Butters R, Gao P, Cantor TL, Kifor I, Brown EM, Wysolmerski J. A Syndrome of Hypocalciuric Hypercalcemia Caused by Autoantibodies Directed at the Calcium-Sensing Receptor. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 60-72. PMID: 12519831, DOI: 10.1210/jc.2002-020249.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoantibodiesBlood Physiological PhenomenaBlotting, WesternCalciumCell LineEnzyme ActivationExtracellular SpaceFemaleHumansHypercalcemiaImmunoglobulinsInositol PhosphatesMiddle AgedMitogen-Activated Protein KinasesParathyroid GlandsParathyroid HormonePedigreePeptide FragmentsReceptors, Calcium-SensingReceptors, Cell SurfaceSyndromeConceptsPTH-dependent hypercalcemiaFamilial hypocalciuric hypercalcemiaHeterozygous inactivating mutationsHypocalciuric hypercalcemiaPTH releaseParathyroid cellsCaR's extracellular domainPatient seraExtracellular amino terminusAnti-CaR antiserumNormocalcemic control subjectsHuman parathyroid cellsBovine parathyroid cellsCalcium-sensing receptorAnti-CAR antibodyCaR-transfected HEK293 cellsInactivating mutationEffect of serumExtracellular domainAntithyroid antibodiesAutoimmune manifestationsEndocrine dysfunctionControl subjectsBlood calciumCaR gene
2002
The Evolutionary Origins of Maternal Calcium and Bone Metabolism During Lactation
Wysolmerski JJ. The Evolutionary Origins of Maternal Calcium and Bone Metabolism During Lactation. Journal Of Mammary Gland Biology And Neoplasia 2002, 7: 267-276. PMID: 12751891, DOI: 10.1023/a:1022800716196.BooksConceptsLower vertebratesEvolutionary originEutherian mammalsBone metabolismBone resorptionMaternal adaptationDifferent speciesMammalsMaternal calcium homeostasisRenal calcium excretionVertebratesAbsorption of calciumCalcium homeostasisEgg productionMetabolismMaternal calciumCalcium excretionHuman pregnancyMaternal transferCalcium metabolismFetal growthMineral metabolismNursing mothersAdaptationPregnancyTreatment of Osteoporosis and Osteopenia in Long‐term Renal Transplant Patients with Alendronate
Cruz DN, Brickel HM, Wysolmerski JJ, Gundberg CG, Simpson CA, Kliger AS, Lorber MI, Basadonna GP, Friedman AL, Insogna KL, Bia MJ. Treatment of Osteoporosis and Osteopenia in Long‐term Renal Transplant Patients with Alendronate. American Journal Of Transplantation 2002, 2: 62-67. PMID: 12095058, DOI: 10.1034/j.1600-6143.2002.020111.x.Peer-Reviewed Original ResearchConceptsBone mineral densityHigh bone turnoverRenal transplant patientsBone lossBone turnoverTransplant patientsTotal femurLumbar spineLong-term renal transplant patientsLong-term renal transplant recipientsBiochemical markersBiochemical parametersGood renal functionGroup A patientsRenal transplant recipientsBone turnover markersRegional bone mineral densityTreatment of osteoporosisSerum alkaline phosphataseFirst yearBisphosphonate therapyTransplant recipientsAlendronate therapyRenal functionA patients