2002
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone NeoplasmsDisease Models, AnimalFemaleGene ExpressionHypercalcemiaMaleMammary Neoplasms, ExperimentalMiceMice, TransgenicNeoplasm MetastasisParathyroid Hormone-Related ProteinPeptide HormonesTumor Cells, CulturedConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidence
2000
Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade
Nakchbandi I, Weir E, Insogna K, Philbrick W, Broadus A. Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 7296-7300. PMID: 10829073, PMCID: PMC16539, DOI: 10.1073/pnas.110553397.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CommunicationCell DifferentiationCells, CulturedCoculture TechniquesDental SacEpithelial CellsMiceMice, KnockoutOsteoclastsParacrine CommunicationParathyroid Hormone-Related ProteinProteinsConceptsNumber of osteoclastsEffects of PTHrPOsteoclast formationDF cellsBone resorptionFactor expressionOsteoclastic bone resorptionDental follicle cellsHormone-related proteinOsteoclast differentiation factorStellate reticulum cellsOsteoclastogenesis inhibitory factorCoronal tooth surfacesSpontaneous osteoclast formationParacrine cascadeParathyroid hormoneEruption pathwayReticulum cellsPeripheral skeletonTooth eruptionOsteoclast precursorsPTH/PTHrP.Inhibitory factorFunctional osteoclastsCrypt cells
1994
Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing.
Yang KH, dePapp AE, Soifer NE, Dreyer BE, Wu TL, Porter SE, Bellantoni M, Burtis WJ, Insogna KL, Broadus AE. Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing. Biochemistry 1994, 33: 7460-9. PMID: 8003511, DOI: 10.1021/bi00189a054.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsChromatography, AffinityChromatography, High Pressure LiquidCricetinaeCricetulusCulture Media, ConditionedHumansImmunohistochemistryMolecular Sequence DataParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsProtein Processing, Post-TranslationalProteinsTumor Cells, CulturedConceptsHormone-related proteinCarboxy-terminal fragmentCell linesTissue-specific posttranslational processingRat insulinoma cellsDistinct paracrineHuman PTHrP geneHumoral hypercalcemiaMalignant tumorsAutocrine roleRIN cell linesMidregion fragmentPTHrP isoformsMost human cell linesNonmalignant tissuesPhysiological rationalePTHrP geneInsulinoma cellsChinese hamster ovary cellsHuman cell linesHamster ovary cellsSecretory formCellsOvary cellsPosttranslational processing
1993
Macrophage colony‐stimulating factor release and receptor expression in bone cells
Weir E, Horowitz M, Baron R, Centrella M, Kacinski B, Insogna K. Macrophage colony‐stimulating factor release and receptor expression in bone cells. Journal Of Bone And Mineral Research 1993, 8: 1507-1518. PMID: 8304053, DOI: 10.1002/jbmr.5650081214.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone MarrowBone Marrow CellsCell DivisionCells, CulturedColony-Forming Units AssayCulture Media, ConditionedGranulocyte-Macrophage Colony-Stimulating FactorMacrophage Colony-Stimulating FactorMacrophagesMaleOsteoblastsOsteoclastsParathyroid HormoneParathyroid Hormone-Related ProteinProteinsRatsRats, Sprague-DawleyRats, WistarReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedConceptsColony-stimulating factorColony-stimulating activityM-CSFBone resorptionReceptor expressionMature osteoclastsPreincubation of CMColony-stimulating factor releaseHormone-related peptideM-CSF receptor c-FmsMacrophage colony-stimulating factorOsteoblast-osteoclast interactionsM-CSF mRNA levelsBone marrow cellsCSF-1 receptor expressionRat bone marrow cellsReceptor c-fmsROS 17/2.8 cellsParacrine roleImmunohistochemical techniquesRat osteoblastsPTHrP treatmentMarrow cellsFactor releasePTHHuman granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro.
Gutmann JN, Burtis WJ, Dreyer BE, Andrade-Gordon P, Penzias AS, Polan ML, Insogna KL. Human granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro. The Journal Of Clinical Endocrinology & Metabolism 1993, 76: 1314-1318. PMID: 8496323, DOI: 10.1210/jcem.76.5.8496323.Peer-Reviewed Original ResearchMeSH KeywordsBiological AssayCorpus LuteumFemaleFollicular FluidGranulosa CellsHumansImmunoradiometric AssayOvaryParathyroid HormoneParathyroid Hormone-Related ProteinProteinsRibonucleasesConceptsGranulosa-luteal cellsOvarian follicular fluidImmunoradiometric assayHuman granulosa-luteal cellsHuman ovarian follicular fluidCultured granulosa-luteal cellsParathyroid hormone-related proteinSubsequent prospective analysisAdenylate cyclase-stimulating activityHormone-related proteinCyclase-stimulating activityPresence of mRNAPossible paracrineShort-term culturePTHrP levelsNormal mammalian tissuesBasal secretionImmunohistochemical studyFollicular fluidAutocrine rolePTHrP immunoreactivityProspective analysisPTHrPPTHImmunoreactivity
1992
Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types.
Soifer NE, Dee KE, Insogna KL, Burtis WJ, Matovcik LM, Wu TL, Milstone LM, Broadus AE, Philbrick WM, Stewart AF. Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types. Journal Of Biological Chemistry 1992, 267: 18236-18243. PMID: 1517251, DOI: 10.1016/s0021-9258(19)37178-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCarcinoma, Renal CellCell LineElectrophoresis, Polyacrylamide GelFluorescent Antibody TechniqueHumansImmunohistochemistryKidney NeoplasmsKineticsMolecular Sequence DataParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsProtein BiosynthesisProteinsTransfectionConceptsMid-region fragmentCell typesSecretory formBasic amino acid motifHormone-related proteinAmino acid motifsImportant biological functionsAmino acid sequenceExtensive post-translational processingPost-translational processingDifferent cell typesHuman renal carcinoma cellsInterspecies conservationSodium dodecyl sulfate-polyacrylamide gel electrophoresis analysisRenal carcinoma cellsAcid motifGel electrophoresis analysisAcid sequenceBiological functionsParathyroid hormone-related proteinRegion-specific immunoassaysRat insulinoma cellsCell extractsCleavage siteAmino acidsParathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length
Mitnick M, Isales C, Paliwal I, Insogna K. Parathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length. Journal Of Bone And Mineral Research 1992, 7: 887-896. PMID: 1332431, DOI: 10.1002/jbmr.5650070805.Peer-Reviewed Original ResearchConceptsCyclic AMP accumulationPGE2 releaseAMP accumulationCultured fetal rat long bonesFetal rat long bonesSaos-2 cellsBone resorptive actionProstaglandin E2 secretionBone-active cytokineHormone-related proteinPrimary human bone cell culturesRelease of PGE2Prostaglandin E2 releaseEffects of PTHrPRat long bonesForm of PTHrPHuman osteoblast-like cellsMalignancy syndromeE2 secretionHumoral hypercalcemiaBasal secretionPGE2 secretionE2 releaseOsteoblast-like cellsPTHrPSynthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo
Weir E, Terwilliger G, Sartori L, Insogna K. Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo. Calcified Tissue International 1992, 51: 30-34. PMID: 1393774, DOI: 10.1007/bf00296214.Peer-Reviewed Original ResearchConceptsBovine parathyroid hormoneSerum calciumParathyroid hormone-like proteinDaily subcutaneous injectionsPotent bone-resorbing agentHormone-related proteinDose-dependent increaseDry bone weightHighest dose levelHormone-like proteinBone-resorbing agentsBone dry weightLow dosage levelsHumoral hypercalcemiaParathyroid hormoneDihydroxyvitamin DMale SpragueDawley ratsSubcutaneous injectionHuman PTHrPBone calciumAnabolic agentsPTHrP actionDose levelsHigh doses
1991
Immunoaffinity purification of parathyroid hormone‐related protein from bovine milk and human keratinocyte‐conditioned medium
Stewart A, Wu T, Insogna K, Milstone L, Burtis W. Immunoaffinity purification of parathyroid hormone‐related protein from bovine milk and human keratinocyte‐conditioned medium. Journal Of Bone And Mineral Research 1991, 6: 305-311. PMID: 2035357, DOI: 10.1002/jbmr.5650060313.Peer-Reviewed Original ResearchAnimalsChromatography, AffinityChromatography, High Pressure LiquidCulture MediaHumansKeratinocytesMilkNeoplasm ProteinsParathyroid Hormone-Related ProteinProteins
1990
Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase
Brown G, Morris C, Mitnick M, Insogna K. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Journal Of Bone And Mineral Research 1990, 5: 1037-1041. PMID: 1964358, DOI: 10.1002/jbmr.5650051007.Peer-Reviewed Original ResearchConceptsSerum calciumBone resorptionHumoral hypercalcemiaCarbonic anhydrase inhibitorsNephrogenous cyclic AMP excretionCyclic AMP excretionMean serum calciumOsteoclastic bone resorptionDrug-treated animalsLeydig cell tumorMechanism of actionUrine phosphorusUrine calciumSerum phosphorusCell tumorsAcetazolamide treatmentHypercalcemiaSignificant fallFisher ratsObserved hypercalcemiaResorptionDirect inhibitionSignificant riseMalignancyRatsTHE PARATHYROID HORMONE-RELATED PROTEIN STIMULATES HUMAN OSTEOBLAST-LIKE CELLS TO SECRETE A 9,000 DALTON BONERESORBING PROTEIN
Morris CA, Mitnick ME, Weir EC, Horowitz M, Kreider BL, Insogna KL. THE PARATHYROID HORMONE-RELATED PROTEIN STIMULATES HUMAN OSTEOBLAST-LIKE CELLS TO SECRETE A 9,000 DALTON BONERESORBING PROTEIN. Endocrinology 1990, 126: 1783-1786. PMID: 2307127, DOI: 10.1210/endo-126-3-1783.Peer-Reviewed Original ResearchMeSH KeywordsBiological FactorsCell LineChromatography, High Pressure LiquidCulture MediaCytokinesElectrophoresis, Polyacrylamide GelHumansMolecular WeightOsteoblastsParathyroid Hormone-Related ProteinProteinsConceptsParathyroid hormone-related proteinBone-resorbing activityHormone-related proteinBone resorptionPTH/Bone-resorbing cytokinesIL-1GM-CSFSingle fractionSequential reverse-phase HPLCII cellsUntreated cellsKD fractionHuman osteoblast-like cellsResorptionSize-exclusion HPLCNgeqOsteoblast-like cellsSpecific activityCellsKD proteinOsteoblastsReversed-phase HPLCCytokinesPGE2
1989
Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein
Insogna K. Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein. Endocrinology And Metabolism Clinics Of North America 1989, 18: 779-794. PMID: 2673773, DOI: 10.1016/s0889-8529(18)30366-9.BooksMeSH KeywordsAmino Acid SequenceAnimalsBone ResorptionHumansHypercalcemiaMolecular Sequence DataNeoplasm ProteinsNeoplasmsParathyroid Hormone-Related ProteinSyndromeConceptsMalignancy-associated hypercalcemiaHumoral hypercalcemiaRenal tubular calcium reabsorptionParathyroid hormone-related proteinIntense bone resorptionTubular calcium reabsorptionTumor-derived factorsCentral pathogenic roleHormone-related proteinTumor-derived tissueCalcium reabsorptionBone resorptionPathogenic roleCommon causeHypercalcemiaExperimental modelHHMDevelopment of antiseraMalignancyPTHrPAnalysis of mRNAAntiserumPreliminary studySyndromeAmino-terminal polypeptideParathyroid Hormone-Related Protein Modulates the Effect of Transforming Growth Factor-β on Deoxyribonucleic Acid and Collagen Synthesis in Fetal Rat Bone Cells*
CENTRELLA M, CANALIS E, MCCARTHY TL, STEWART AF, ORLOFF JJ, INSOGNA KL. Parathyroid Hormone-Related Protein Modulates the Effect of Transforming Growth Factor-β on Deoxyribonucleic Acid and Collagen Synthesis in Fetal Rat Bone Cells*. Endocrinology 1989, 125: 199-208. PMID: 2737143, DOI: 10.1210/endo-125-1-199.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesCells, CulturedCollagenDNAFetusNeoplasm ProteinsOrgan Culture TechniquesParathyroid HormoneParathyroid Hormone-Related ProteinRatsRats, Inbred StrainsTransforming Growth FactorsNative and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties.
Insogna KL, Stewart AF, Morris CA, Hough LM, Milstone LM, Centrella M. Native and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties. Journal Of Clinical Investigation 1989, 83: 1057-1060. PMID: 2537846, PMCID: PMC303783, DOI: 10.1172/jci113947.Peer-Reviewed Original ResearchMeSH KeywordsCell Transformation, NeoplasticCyclic AMPEpidermal Growth FactorFibroblastsFibronectinsHumansNeoplasm ProteinsParathyroid HormoneParathyroid Hormone-Related ProteinTransforming Growth FactorsConceptsGrowth factor-like propertiesParathyroid hormone-like proteinHormone-like proteinNRK-49F cellsParaneoplastic syndromeHumoral hypercalcemiaLatter hormoneHuman tumorsPhysiological actionsPTHHuman dermal fibroblastsSignificant increaseSoft agarDisplay actionsDermal fibroblastsSynthetic peptidesSynthetic analoguesHypercalcemiaMalignancySyndromeTumorsUnique primary structureSynthetic Parathyroid Hormone-Like Protein-(1–74): Biochemical and Physiological Characterization*
STEWART A, ELLIOT J, BURTIS W, WU T, INSOGNA K. Synthetic Parathyroid Hormone-Like Protein-(1–74): Biochemical and Physiological Characterization*. Endocrinology 1989, 124: 642-648. PMID: 2912692, DOI: 10.1210/endo-124-2-642.Peer-Reviewed Original ResearchConceptsAmino acid compositionDirect amino acid sequencingAmino acid sequencingAcid compositionPhysiological characterizationN-terminusParathyroid hormone-like proteinRenal cortical adenylate cyclaseFetal rat long bonesInternal sequencesTransduction mechanismsCortical adenylate cyclasePhysiological comparisonPTH-like proteinHormone-like proteinProteolytic fragmentsRat long bonesAdenylate cyclase assayBovine PTHProteinPTH receptorFull-length peptidePeptide hormonesSynthetic peptidesNovel classSynthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*
THORIKAY M, KRAMER S, REYNOLDS F, SORVILLO J, DOESCHER L, WU T, MORRIS C, BURTIS W, INSOGNA K, VALENZUELA D, STEWART A. Synthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*. Endocrinology 1989, 124: 111-118. PMID: 2535801, DOI: 10.1210/endo-124-1-111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBiological AssayBone and BonesCalciumCloning, MolecularCyclic AMPDNADogsEscherichia coliGenes, SyntheticKidneyMolecular Sequence DataMolecular WeightNeoplasm ProteinsOsteosarcomaParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsPlasmidsRatsRecombinant ProteinsTumor Cells, Cultured
1988
Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*
Weir EC, Burtis WJ, Morris CA, Brady TG, Insogna KL. Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*. Endocrinology 1988, 123: 2744-2751. PMID: 3197642, DOI: 10.1210/endo-123-6-2744.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAmino Acid SequenceAmino AcidsAnimalsDogsHumansHypercalcemiaLeydig Cell TumorMaleMolecular Sequence DataMolecular WeightNeoplasm ProteinsNeoplasmsParathyroid Hormone-Related ProteinRatsRats, Inbred F344Sequence Homology, Nucleic AcidSweat Gland NeoplasmsTesticular NeoplasmsConceptsPTH-like proteinAnimal tumorsPTH-like peptideHumoral hypercalcemiaParathyroid hormone-like proteinSynthetic human PTHLeydig cell tumorHuman PTH-like peptideHormone-like proteinTransplantable animal tumorsCell adenocarcinomaCanine proteinCell tumorsResponsible mediatorsHuman PTHImmunoradiometric assayTumorsHuman tumorsAdenylate cyclaseLike peptidesAnal sacHypercalcemiaBone cellsMalignancyPotent activatorCharacterization of a parathyroid Hormonelike Peptide Secreted by Human Keratinocytes
INSOGNA K, STWART A, IKEDA K, CENTRELLA M, MILSONE L. Characterization of a parathyroid Hormonelike Peptide Secreted by Human Keratinocytes. Annals Of The New York Academy Of Sciences 1988, 548: 146-159. PMID: 2470290, DOI: 10.1111/j.1749-6632.1988.tb18801.x.Peer-Reviewed Original ResearchHumoral Hypercalcemia of Cancer
Flier J, Underhill L, Broadus A, Mangin M, Ikeda K, Insogna K, Weir E, Burtis W, Stewart A. Humoral Hypercalcemia of Cancer. New England Journal Of Medicine 1988, 319: 556-563. PMID: 3043221, DOI: 10.1056/nejm198809013190906.BooksAnimalsHumansHypercalcemiaNeoplasm ProteinsNeoplasmsParaneoplastic SyndromesParathyroid HormoneParathyroid Hormone-Related ProteinIdentification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.
Ikeda K, Mangin M, Dreyer BE, Webb AC, Posillico JT, Stewart AF, Bander NH, Weir EC, Insogna KL, Broadus AE. Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy. Journal Of Clinical Investigation 1988, 81: 2010-2014. PMID: 2454953, PMCID: PMC442656, DOI: 10.1172/jci113551.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCloning, MolecularHumansHypercalcemiaKidney NeoplasmsMolecular Sequence DataNeoplasm ProteinsNucleic Acid HybridizationParaneoplastic SyndromesParathyroid HormoneParathyroid Hormone-Related ProteinPoly ARNARNA, MessengerRNA, NeoplasmSequence Homology, Nucleic AcidTranscription, GeneticConceptsPTH-like peptideParathyroid hormone-like peptideAnimal tumorsHumoral hypercalcemiaHormone-like peptideSyndrome of HHMVariety of humanHuman PTH-like peptideSimilar histological typeHistological typeHuman PTHTumor typesTumorsHHMHypercalcemiaMalignancySyndromeMessenger RNAMRNAWide spectrumHumansPeptidesMammalian speciesRNAPTH