2014
Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss
Lee Y, Brown EJ, Chang S, McKinnon PJ. Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss. Journal Of Neuroscience 2014, 34: 7836-7844. PMID: 24899707, PMCID: PMC4044246, DOI: 10.1523/jneurosci.4245-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAtaxia Telangiectasia Mutated ProteinsBeta-GalactosidaseBrainCell CycleCell Cycle ProteinsCells, CulturedDNA DamageDNA-Binding ProteinsEmbryo, MammalianFemaleGene Expression RegulationMaleMiceMice, TransgenicNestinNeuronsShelterin ComplexTelomereTelomere-Binding Proteins
2013
p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses
Wang Y, Sharpless N, Chang S. p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses. Journal Of Clinical Investigation 2013, 123: 4489-4501. PMID: 24091330, PMCID: PMC3784543, DOI: 10.1172/jci69574.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBone Marrow TransplantationCell ProliferationCells, CulturedCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21DNA DamageDNA RepairDNA-Binding ProteinsFemaleHematopoiesisHematopoietic Stem CellsIntestine, SmallMaleMiceMice, SCIDMice, TransgenicProtein StabilitySequence DeletionSpleenTelomereTelomere HomeostasisTumor Suppressor Protein p53ConceptsHematopoietic cellsDeletion of p21P21-dependent cell cycle arrestOrgan impairmentTelomere dysfunctionCell cycle arrestMouse modelDNA damage responseSmall intestineFunctional defectsCell functionProliferative capacityP53-dependent apoptosisCycle arrestDysfunctional telomeresCellular senescenceDysfunctionP53-dependent DNA damage responseProliferative cellsHematopoietic systemProtective functionTumor suppressorProliferative defectP53 stabilizationCells
2012
Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis
Akbay EA, Peña CG, Ruder D, Michel JA, Nakada Y, Pathak S, Multani AS, Chang S, Castrillon DH. Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis. Oncogene 2012, 32: 2211-2219. PMID: 22689059, PMCID: PMC3636499, DOI: 10.1038/onc.2012.232.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyAnimalsCarcinoma, EndometrioidCell Transformation, NeoplasticDisease Models, AnimalDNA Breaks, Double-StrandedDNA-Binding ProteinsEndometrial NeoplasmsFemaleHumansMiceMice, TransgenicShelterin ComplexTelomere HomeostasisTelomere-Binding ProteinsTumor Cells, CulturedTumor Suppressor Protein p53ConceptsType II endometrial cancerEndometrial intraepithelial carcinomaEndometrial cancerEndometrial adenocarcinomaEndometrial carcinogenesisTelomerase-null miceProminent nuclear atypiaType II tumorsMulti-organ failureType II cancersInvasive endometrial adenocarcinomaMonths of ageMetastatic diseaseII tumorsEndometrial lesionsIntraepithelial carcinomaEndometrial epitheliumNuclear atypiaTumorsAdenocarcinomaVivo correlatesDetectable DNA damageHuman tumorsMiceLesions
2011
Essential roles for Pot1b in HSC self-renewal and survival
Wang Y, Shen MF, Chang S. Essential roles for Pot1b in HSC self-renewal and survival. Blood 2011, 118: 6068-6077. PMID: 21948176, PMCID: PMC3234665, DOI: 10.1182/blood-2011-06-361527.Peer-Reviewed Original ResearchAgingAnemia, AplasticAnimalsApoptosisBone Marrow CellsBone Marrow DiseasesBone Marrow Failure DisordersCell DifferentiationCell SurvivalCells, CulturedChromosomes, MammalianDNA DamageDNA-Binding ProteinsFemaleHematopoietic Stem CellsHemoglobinuria, ParoxysmalMaleMiceMice, Inbred ICRMice, Mutant StrainsMice, SCIDTelomereTumor Suppressor Protein p53
2010
The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development
Akhter S, Lam YC, Chang S, Legerski RJ. The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development. Aging Cell 2010, 9: 1047-1056. PMID: 20854421, PMCID: PMC3719988, DOI: 10.1111/j.1474-9726.2010.00631.x.Peer-Reviewed Original ResearchConceptsMutant mouse embryonic fibroblastsSNM1B/ApolloCell proliferation defectMouse embryonic fibroblastsNormal cell proliferationDevelopmental failureHomozygous null miceEnd fusionsProliferation defectEmbryonic developmentGenomic instabilityEmbryonic fibroblastsTelomeric endDevelopmental defectsCell deathVivo roleCell proliferationImpaired proliferationTelomeresNull miceMutant miceAurora Kinase A Promotes Ovarian Tumorigenesis through Dysregulation of the Cell Cycle and Suppression of BRCA2
Yang G, Chang B, Yang F, Guo X, Cai K, Xiao X, Wang H, Sen S, Hung M, Mills G, Chang S, Multani A, Mercado-Uribe I, Liu J. Aurora Kinase A Promotes Ovarian Tumorigenesis through Dysregulation of the Cell Cycle and Suppression of BRCA2. Clinical Cancer Research 2010, 16: 3171-3181. PMID: 20423983, PMCID: PMC2930838, DOI: 10.1158/1078-0432.ccr-09-3171.Peer-Reviewed Original ResearchConceptsDNA damage responseGenomic instabilitySmall hairpin RNADamage responseExpression ratioCell cycle progressionOvarian cancer cell line SKOV3Multiple human cancersColon cancer samplesKnockdown of AuroraCell cycle alterationsMitotic spindleCell cycle dysregulationCell line SKOV3Cycle progressionExpression of AuroraMolecular mechanismsCell cycleAurora kinasesHairpin RNATumor growthCentrosome amplificationHuman cancersHuman ovarian cancerHigh-grade ovarian serous carcinoma
2007
Overexpression of the Low Molecular Weight Cyclin E in Transgenic Mice Induces Metastatic Mammary Carcinomas through the Disruption of the ARF-p53 Pathway
Akli S, Van Pelt CS, Bui T, Multani AS, Chang S, Johnson D, Tucker S, Keyomarsi K. Overexpression of the Low Molecular Weight Cyclin E in Transgenic Mice Induces Metastatic Mammary Carcinomas through the Disruption of the ARF-p53 Pathway. Cancer Research 2007, 67: 7212-7222. PMID: 17671189, DOI: 10.1158/0008-5472.can-07-0599.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsApoptosisBlotting, WesternCyclin ECyclin-Dependent Kinase Inhibitor p16FemaleGene Expression Regulation, NeoplasticGene SilencingHumansImmunoenzyme TechniquesIn Situ Nick-End LabelingLoss of HeterozygosityLung NeoplasmsMammary Neoplasms, ExperimentalMiceMice, KnockoutMice, TransgenicMutationPolymerase Chain ReactionTumor Cells, CulturedTumor Suppressor Protein p53ConceptsFull-length cyclin ECyclin E overexpressionCyclin EARF-p53 pathwayTransgenic miceLow molecular weight cyclin EE overexpressionMetastatic mammary carcinomaMammary tumor formationWeight cyclin ETumor-bearing animalsBreast cancer tumorigenesisBreast cancer cellsMouse mammary tumor virus promoterLow molecular weight isoformsLMW formsOncologic roleInactivation of p53Mammary carcinomaBreast cancerMammary adenocarcinomaLoss of heterozygosityCancer tumorigenesisMammary epithelial cellsMolecular weight isoforms
2004
Essential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nature Genetics 2004, 36: 877-882. PMID: 15235603, DOI: 10.1038/ng1389.Peer-Reviewed Original ResearchConceptsWerner syndromeCultured cellsComplex cellular phenotypesElevated genomic instabilityDNA damage fociPremature aging syndromesWRN deficiencyReplicative senescenceCellular phenotypesGenomic instabilityAging syndromesGenetic dataMutational inactivationPremature senescenceChromosomal instabilityTelomerase expressionHair grayingPremature agingDisease phenotypeEssential roleWRNMice nullSenescenceAutosomal recessive diseaseType II diabetesTumor-Specific Low Molecular Weight Forms of Cyclin E Induce Genomic Instability and Resistance to p21, p27, and Antiestrogens in Breast Cancer
Akli S, Zheng PJ, Multani AS, Wingate HF, Pathak S, Zhang N, Tucker SL, Chang S, Keyomarsi K. Tumor-Specific Low Molecular Weight Forms of Cyclin E Induce Genomic Instability and Resistance to p21, p27, and Antiestrogens in Breast Cancer. Cancer Research 2004, 64: 3198-3208. PMID: 15126360, DOI: 10.1158/0008-5472.can-03-3672.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsBreast NeoplasmsCDC2-CDC28 KinasesCell Cycle ProteinsCell DivisionCell Line, TumorCyclin ECyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent Kinase Inhibitor p27CyclinsEstradiolEstrogen Receptor ModulatorsFemaleFulvestrantG1 PhaseGenomic InstabilityHumansMiddle AgedMolecular WeightPolyploidyProtein IsoformsTransfectionTumor Suppressor ProteinsConceptsBreast cancer patientsPoor outcomeCancer patientsBreast cancerCyclin ELMW formsPoor clinical outcomeEffects of antiestrogensPotential therapeutic targetLow molecular weight isoformsCyclin-dependent kinase inhibitor p21Clinical outcomesAggressive diseaseSurrogate markerDisease progressionPathobiological mechanismsTherapeutic targetMolecular weight isoformsPatientsTumor cellsLMW isoformsTumorsPowerful predictorLow molecular weight formWeight isoformsEndogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects
Tuveson D, Shaw A, Willis N, Silver D, Jackson E, Chang S, Mercer K, Grochow R, Hock H, Crowley D, Hingorani S, Zaks T, King C, Jacobetz M, Wang L, Bronson R, Orkin S, DePinho R, Jacks T. Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 2004, 5: 375-387. PMID: 15093544, DOI: 10.1016/s1535-6108(04)00085-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell DivisionCell Transformation, NeoplasticCellular SenescenceCongenital AbnormalitiesCrosses, GeneticCyclin-Dependent Kinase Inhibitor p16Embryo, MammalianFemaleFibroblastsGene Expression Regulation, DevelopmentalGenes, rasIntegrasesMaleMiceMice, Inbred C57BLMice, TransgenicMutationNeoplasmsStem CellsTumor Suppressor Protein p14ARFTumor Suppressor Protein p53Viral ProteinsConceptsCanonical Ras effectorRas effectorsOncogenic RasEmbryonic developmentAbnormal cellular proliferationDevelopmental defectsRas oncogeneGenetic lesionsConditional expressionWidespread expressionK-RasG12DCellular proliferationFurther genetic abnormalitiesEnhanced proliferationOncogeneProliferationExpressionGenetic abnormalitiesEffectorsMutationsAllelesRegulationPathwayFibroblastsFrank malignancy
2000
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi S, Chang S, Lee S, Alson S, Gottlieb G, Chin L, DePinho R. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 2000, 406: 641-645. PMID: 10949306, DOI: 10.1038/35020592.Peer-Reviewed Original ResearchConceptsEpithelial cancersSoft tissue sarcomasTelomere lengthP53 mutant miceTumor suppressor gene mutationsSuppressor gene mutationsNon-reciprocal translocationsTissue sarcomasTelomere dysfunctionAged humansMutant miceCytogenetic featuresCancerMiceHuman carcinomasGene mutationsEpithelial renewalTelomerase expressionCritical reductionCarcinomaDysfunctionHigh rateReverse transcriptaseEukaryotic chromosomesNucleoprotein complexes