2016
Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016, 29: 255-269. PMID: 26977878, PMCID: PMC4794996, DOI: 10.1016/j.ccell.2016.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesNeoplasm Recurrence, LocalPhosphorylationProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsHER2-positive breast cancerCDK4/6 inhibitorsBreast cancerEGFR/HER2Patient-derived xenograft tumorsTransgenic mouse modelInhibition of CDK4/6Tumor recurrenceXenograft tumorsMouse modelPotent suppressionTransgenic modelClinical specimensTherapeutic resistanceDual inhibitionMediate resistanceHER2CancerTSC2 phosphorylationG1 arrestCellular senescenceTherapyRb phosphorylationTumorsCDK4/6
2005
HIN-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
2004
Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types.
Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J, Batra SK, Papadopoulos N, Richards WG, Sugarbaker DJ, Wright RL, Shim J, Stamey TA, Sellers WR, Loda M, Meyerson M, Hruban R, Jen J, Polyak K. Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Molecular Cancer Research 2004, 2: 489-94. PMID: 15383627, DOI: 10.1158/1541-7786.489.2.9.Peer-Reviewed Original ResearchConceptsHIN-1 expressionHIN-1 methylationHIN-1Breast carcinomaPancreatic carcinomaSmall cell lung cancerNormal tissuesMajority of lungCell lung cancerSquamous cell carcinomaMultiple human cancer typesPromoter methylationMultiple human tumor typesBronchial epithelial cellsHuman cancer typesHuman tumor typesNoncancer patientsCell carcinomaPromoter methylation statusLung cancerBronchial lavagePremalignant changesLack of expressionLung carcinomaProstate tumors
2003
Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors.
Krop I, Maguire P, Lahti-Domenici J, Lodeiro G, Richardson A, Johannsdottir HK, Nevanlinna H, Borg A, Gelman R, Barkardottir RB, Lindblom A, Polyak K. Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors. Cancer Research 2003, 63: 2024-7. PMID: 12727813.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCytokinesDNA MethylationDNA, NeoplasmFemaleGenes, BRCA1Genes, Tumor SuppressorGenetic Predisposition to DiseaseGerm-Line MutationHumansTumor Suppressor ProteinsConceptsHIN-1 methylationBreast tumorsHIN-1BRCA1 tumorsSporadic breast tumorsFamilial breast cancer patientsBreast cancer patientsSpecific breast cancer subtypesBreast cancer riskBreast cancer subtypesSporadic breast carcinomasGerm-line mutationsPromoter methylation statusCancer patientsHER2 statusBreast carcinomaHistopathological phenotypeEstrogen receptorCancer riskCandidate tumor suppressor geneCancer subtypesSporadic casesTumorsCancer typesTumor suppressor gene
2001
HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells
Krop I, Sgroi D, Porter D, Lunetta K, LeVangie R, Seth P, Kaelin C, Rhei E, Bosenberg M, Schnitt S, Marks J, Pagon Z, Belina D, Razumovic J, Polyak K. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 9796-9801. PMID: 11481438, PMCID: PMC55532, DOI: 10.1073/pnas.171138398.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernBlotting, WesternBreastBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingCarcinoma, LobularCell DivisionCells, CulturedChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusCytokinesDNA MethylationEpithelial CellsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene LibraryGene SilencingGenes, Tumor SuppressorGrowth InhibitorsHumansMolecular Sequence DataNeoplasm ProteinsPromoter Regions, GeneticRecombinant Fusion ProteinsRNA, MessengerRNA, NeoplasmSequence AlignmentSequence Homology, Amino AcidTransfectionTumor Cells, CulturedTumor Suppressor ProteinsConceptsHIN-1 expressionHIN-1Mammary epithelial cellsPutative cytokineEpithelial cellsBreast cancer cell linesHuman breast carcinomaCancerous mammary epithelial cellsBreast cancer cellsCancer cell linesDuctal carcinomaLobular carcinomaPrimary tumorPreinvasive lesionsBreast carcinomaCandidate tumor suppressor geneMolecular alterationsTumor suppressor geneCarcinomaCancer cellsGene expression profilesCell linesCytokinesSuppressor geneCell growth