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
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 expression
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
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.BooksMeSH KeywordsAnimalsBreastEpithelial CellsFemaleHumansLactationMammary Glands, AnimalMammary Glands, HumanParathyroid Hormone-Related ProteinReceptors, Calcium-SensingSignal TransductionConceptsG-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 markersOverexpressionParathyroid Hormone-Related Protein: An Update
Wysolmerski JJ. Parathyroid Hormone-Related Protein: An Update. The Journal Of Clinical Endocrinology & Metabolism 2012, 97: 2947-2956. PMID: 22745236, PMCID: PMC3431578, DOI: 10.1210/jc.2012-2142.BooksMeSH KeywordsAnimalsCell NucleusHumansParathyroid DiseasesParathyroid HormoneParathyroid Hormone-Related ProteinProtein ConformationReceptors, Parathyroid HormoneConceptsType 1 PTH/PTHrP receptorPTH/PTHrP receptorCauses of hypercalcemiaCommon paraneoplastic syndromeParaneoplastic syndromeHumoral hypercalcemiaParathyroid hormonePTHrP receptorBreast cancerNormal physiological functionPTHrPDisease statesTranslational researchHypercalcemiaOsteoporosisBedsidePhysiological functionsRelated genesHyperparathyroidismBasic biologyDiabetesMalignancyOsteoarthritisSyndromePTHPTHrP 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.BooksMeSH KeywordsAnimalsBreast NeoplasmsChromosomes, Human, Pair 12Chromosomes, Human, Pair 21FemaleGenetic LociGenetic Predisposition to DiseaseHumansMammary Neoplasms, ExperimentalNeoplasm MetastasisParathyroid Hormone-Related ProteinConceptsBone 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
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 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 ResearchMeSH KeywordsAnimalsBone and BonesBone DensityEstrogensFemaleFertility Agents, FemaleLactationLeuprolideMiceOvariectomyParathyroid Hormone-Related ProteinConceptsBone mineral densityBone lossEstrogen deficiencyMineral densityInfusion of PTHrPReversible bone lossLevels of estrogenCombination of OVXLeuprolide treatmentCentral hypogonadismGnRH agonistMaternal skeletonBone turnoverOsmotic minipumpsOsteoclast numberBone metabolismBone resorptionSurgical ovariectomyNulliparous micePTHrPOVXInfusionEstrogenLeuprolideModest decline
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 ResearchMeSH KeywordsAdrenocorticotropic HormoneAnimalsCell LineCyclic AMPGTP-Binding Protein alpha Subunits, GsMiceParathyroid Hormone-Related ProteinPituitary GlandReceptors, Calcium-SensingConceptsG 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
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
BMP4 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 ResearchMeSH KeywordsAnimalsBiological TransportCalciumFemaleHaplotypesLactationMammary Glands, AnimalMiceMice, KnockoutMilkParathyroid Hormone-Related ProteinReceptors, Calcium-SensingConceptsCalcium-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 confirmationReceptorsSecretionHypercalcemia of Malignancy due to Ectopic Transactivation of the Parathyroid Hormone Gene
VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R. Hypercalcemia of Malignancy due to Ectopic Transactivation of the Parathyroid Hormone Gene. The Journal Of Clinical Endocrinology & Metabolism 2005, 91: 580-583. PMID: 16263810, DOI: 10.1210/jc.2005-2095.Peer-Reviewed Original ResearchMeSH KeywordsAgedDNA MethylationDNA, NeoplasmFatal OutcomeFemaleGene ExpressionHumansHypercalcemiaHyperparathyroidismNeuroendocrine TumorsPancreatic NeoplasmsParathyroid GlandsParathyroid Hormone-Related ProteinPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionTranscriptional ActivationContinuous 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 ResearchMeSH KeywordsAdultBone Density Conservation AgentsCalcitriolCalciumFemaleHumansHypercalcemiaMaleOsteoblastsOsteogenesisParathyroid Hormone-Related ProteinTeriparatideConceptsContinuous 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 resorptionKey stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland
Hens JR, Wysolmerski JJ. Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Research 2005, 7: 220. PMID: 16168142, PMCID: PMC1242158, DOI: 10.1186/bcr1306.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBreastEmbryonic DevelopmentEpidermal CellsEpidermisFemaleHumansLactationMammary Glands, AnimalMesodermMiceMilkMorphogenesisParathyroid Hormone-Related ProteinConceptsMammary gland developmentEmbryonic mammary glandGland developmentMolecular mechanismsEmbryonic mammary gland developmentMammary glandProtein signalingMore genesFibroblast growth factorSignaling pathwaysFunctional roleGrowth factorWntGenesKey stagesSignalingMesenchymePathwayMechanismGlandEpidermisDevelopment