2014
Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A
Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e3062-e3071. PMID: 25024194, PMCID: PMC4121806, DOI: 10.1073/pnas.1411370111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCyclin-Dependent Kinase Inhibitor p21HumansMiceMice, NudeMutationNeoplasms, ExperimentalTelomeraseTumor Suppressor Protein p53ConceptsP53-mediated transcriptional activationCyclin-dependent kinase inhibitor 1AMutant p53Telomerase inhibitionTumor suppressor p53Transcriptional activationSynergistic tumor suppressionTelomere dysfunctionCheckpoint proteinsP53 upregulated modulatorTumor suppressionCDK inhibitorsSuppressor p53Inhibitor 1AP53 activityTelomeraseHuman cancersCancer cell linesApoptosis inductionPharmacological inhibitionApoptosisCell linesPharmacological restorationP21Growth inhibition
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
2008
Telomere dysfunction and tumour suppression: the senescence connection
Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nature Reviews Cancer 2008, 8: 450-458. PMID: 18500246, PMCID: PMC3688269, DOI: 10.1038/nrc2393.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCellular SenescenceCyclin-Dependent Kinase Inhibitor p21DNA DamageHumansNeoplasmsRetinoblastoma ProteinTelomeraseTelomereTumor Suppressor Protein p53ConceptsTelomere dysfunctionDysfunctional telomeresDNA damage responseKey PointsTelomeresEukaryotic chromosomesGenome instabilityShelterin complexApoptotic programDamage responseRepetitive sequencesCellular senescenceTelomeric endTumor suppressionProtein resultsP53 pathwayMutant p53TelomeresSpontaneous tumorigenesisSenescenceTumorigenesisMouse modelChromosomesDysfunctionProteinApoptosis
2004
Tumor-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 isoforms