2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMice
2005
A Putative Role for Psoriasin in Breast Tumor Progression
Krop I, März A, Carlsson H, Li X, Bloushtain-Qimron N, Hu M, Gelman R, Sabel MS, Schnitt S, Ramaswamy S, Kleer CG, Enerbäck C, Polyak K. A Putative Role for Psoriasin in Breast Tumor Progression. Cancer Research 2005, 65: 11326-11334. PMID: 16357139, DOI: 10.1158/0008-5472.can-05-1523.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBreast NeoplasmsCalcium-Binding ProteinsCarcinoma, Intraductal, NoninfiltratingCollagenasesDisease ProgressionDown-RegulationFemaleHumansMatrix Metalloproteinase 13MiceMice, NudeNeovascularization, PathologicReceptors, EstrogenRNA, MessengerRNA, Small InterferingS100 Calcium Binding Protein A7S100 ProteinsTumor Cells, CulturedVascular Endothelial Growth Factor AConceptsReactive oxygen speciesInvasive breast carcinomaBreast tumor progressionVascular endothelial growth factorTumor progressionMitochondrial reactive oxygen speciesPsoriasin expressionStable short hairpin RNAShort hairpin RNAAnti-invasive functionPutative functionsHuman IBC cell linesEstrogen receptor-negative tumorsHuman invasive breast carcinomasHairpin RNAHigh psoriasin expressionIBC cell linesWorse clinical outcomesCell migrationPoor prognostic factorReceptor-negative tumorsPutative roleInhibits tumor growthMatrix metalloproteinase-13Cell proliferationHIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation
Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K. HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation. Cancer Research 2005, 65: 9659-9669. PMID: 16266985, DOI: 10.1158/0008-5472.can-05-1663.Peer-Reviewed Original ResearchConceptsTumor suppressor functionHIN-1Suppressor functionMitogen-induced phosphorylationCell growthPotential tumor suppressor functionAnchorage-independent cell growthCell cycle reentryActivation of AktCell cycle arrestActivates AktRetinoblastoma proteinHIN-1 geneGrowth arrestAkt activationRb phosphorylationApparent cell cycle arrestLigand-binding studiesCell migrationCycle arrestPhosphorylationAktEpithelial cellsProteinPotent inhibitor