2022
p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade
Molkentine DP, Molkentine JM, Bridges KA, Valdecanas DR, Dhawan A, Bahri R, Hefner AJ, Kumar M, Yang L, Abdelhakiem M, Pifer PM, Sandulache V, Sheth A, Beadle BM, Thames HD, Mason KA, Pickering CR, Meyn RE, Skinner HD. p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade. Cancer Research 2022, 82: 916-928. PMID: 34965932, PMCID: PMC9136619, DOI: 10.1158/0008-5472.can-21-2101.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCarrier ProteinsCyclin-Dependent Kinase Inhibitor p16DNA DamageDNA, ViralHead and Neck NeoplasmsHumansPapillomaviridaePapillomavirus InfectionsSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific Peptidase 7ConceptsUbiquitin-specific protease 7DNA damage repairDamage repairHPV-positive tumorsTranscription factor Sp1Human papillomavirusFactor Sp1Neck squamous cell carcinoma cellsDNA-damaging therapiesRenders cellsHomologous recombinationSignaling cascadesHPV-negative diseaseSquamous cell carcinoma cellsHPV-negative counterpartsHPV-positive diseaseSquamous cell carcinomaUSP7 inhibitorsDNA damageHPV-negative HNSCCFunctional roleDegradation pathwayHPV positivityPathwayUndiscovered pathways
2021
Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor
Gorur A, Patiño M, Shi T, Corrales G, Takahashi H, Rangel R, Gleber‐Netto F, Pickering C, Myers JN, Cata JP. Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor. Journal Of Cellular Physiology 2021, 236: 7698-7710. PMID: 34038587, DOI: 10.1002/jcp.30421.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHead and Neck NeoplasmsHumansMaleMice, Inbred C57BLMice, NudeNaltrexoneNarcotic AntagonistsNeoplasm InvasivenessQuaternary Ammonium CompoundsReceptors, Opioid, muSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor BurdenXenograft Model Antitumor AssaysConceptsMu-opioid receptorsEffects of methylnaltrexoneHNSCC cell linesTumor growthCell linesNeck squamous cell carcinoma growthNeck squamous cell carcinomaDifferent HNSCC cell linesClonogenic activitySquamous cell carcinoma growthSquamous cell carcinomaLung cancer cell linesCyclic adenosine monophosphate levelsTumor-bearing miceAggressive cell behaviorEpithelial-mesenchymal transitionAdenosine monophosphate levelsCancer cell linesCell carcinomaMethylnaltrexoneCarcinoma growthTherapeutic targetLow dosesFaDu cellsMetastasis formation
2019
PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition
Sambandam V, Frederick MJ, Shen L, Tong P, Rao X, Peng S, Singh R, Mazumdar T, Huang C, Li Q, Pickering CR, Myers JN, Wang J, Johnson FM. PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition. Clinical Cancer Research 2019, 25: 3329-3340. PMID: 30770351, PMCID: PMC6548600, DOI: 10.1158/1078-0432.ccr-18-3276.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCRISPR-Cas SystemsDisease Models, AnimalDose-Response Relationship, DrugGene EditingGene ExpressionGene Knockdown TechniquesHumansLoss of Function MutationMicePhosphatidylinositol 3-KinasesProtein Kinase InhibitorsPyruvate Dehydrogenase Acetyl-Transferring KinaseReceptor, Notch1Signal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesConceptsPI3K/mTOR inhibitorPI3K/mTOR inhibitionPI3K/mTOR pathway inhibitorsMTOR pathway inhibitorsHNSCC cell linesMTOR inhibitorsMTOR inhibitionCell linesPathway inhibitorNeck squamous cell carcinomaDrug-sensitive cell linesClinical response ratePI3K/mTOR pathwaySquamous cell carcinomaBiomarkers of responseOrthotopic xenograft modelCell carcinomaTumor sizeXenograft modelHNSCCSingle agentPDK1 overexpressionResponse rateMolecular vulnerabilitiesPharmacogenomic approach
2017
Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer
Skinner HD, Giri U, Yang LP, Kumar M, Liu Y, Story MD, Pickering CR, Byers LA, Williams MD, Wang J, Shen L, Yoo SY, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer. Clinical Cancer Research 2017, 23: 2713-2722. PMID: 28476872, PMCID: PMC5457365, DOI: 10.1158/1078-0432.ccr-16-2586.Peer-Reviewed Original ResearchMeSH KeywordsAgedAxl Receptor Tyrosine KinaseB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedPapillomaviridaePhosphatidylinositol 3-KinasesProteomicsProto-Oncogene ProteinsRadiation ToleranceReceptor Protein-Tyrosine KinasesRNA, MessengerSignal TransductionConceptsPD-L1HPV-negative HNSCC tumorsNeck squamous cell carcinomaCell linesHPV-negative HNSCC cell linesLocal failureLocal treatment failurePD-L1 axisPD-L1 expressionTumor-infiltrating lymphocytesSquamous cell carcinomaHuman papilloma virusLow expression groupActivation of AxlHNSCC cell linesClin Cancer ResNegative cell linesTreatment failureCell carcinomaPapilloma virusHNSCC tumorsExpression groupMultivariate analysisMRNA expression analysisPI3-kinaseMutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors
Zhang M, Singh R, Peng S, Mazumdar T, Sambandam V, Shen L, Tong P, Li L, Kalu NN, Pickering CR, Frederick M, Myers JN, Wang J, Johnson FM. Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors. Cancer Letters 2017, 392: 71-82. PMID: 28126323, PMCID: PMC5404895, DOI: 10.1016/j.canlet.2017.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 1Checkpoint Kinase 2Dose-Response Relationship, DrugG2 Phase Cell Cycle CheckpointsGenotypeHead and Neck NeoplasmsHumansLIM Domain ProteinsMice, NudeMolecular Targeted TherapyMutationNuclear ProteinsPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPteridinesPyrazolesPyrimidinesPyrimidinonesRas ProteinsRNA InterferenceSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckThiophenesTime FactorsTransfectionTumor BurdenUreaXenograft Model Antitumor AssaysConceptsPolo-like kinase 1Cell linesLIM protein AjubaHNSCC cell linesInhibitor-induced apoptosisProtein expressionCell cycle inhibitorsCell cycle arrestKnockdown of PLK1Neck squamous cell carcinomaAjubaExogenous expressionNeck squamous cell carcinoma (HNSCC) tumorsSquamous cell carcinoma tumorsKinase 1HNSCC mouse modelSquamous cell carcinomaSubstrate inhibitionHigher drug dosesPotential candidate biomarkersGenomic alterationsMitotic inhibitorsPLK1 inhibitionSensitive cell linesMutations
2015
Comprehensive genomic characterization of head and neck squamous cell carcinomas
Lawrence M, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel S, Getz G, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, Butterfield Y, Carlsen R, Cheng D, Chu A, Dhalla N, Guin R, Holt R, Jones S, Lee D, Li H, Marra M, Mayo M, Moore R, Mungall A, Gordon Robertson A, Schein J, Sipahimalani P, Tam A, Thiessen N, Wong T, Protopopov A, Santoso N, Lee S, Parfenov M, Zhang J, Mahadeshwar H, Tang J, Ren X, Seth S, Haseley P, Zeng D, Yang L, Xu A, Song X, Pantazi A, Bristow C, Hadjipanayis A, Seidman J, Chin L, Park P, Kucherlapati R, Akbani R, Casasent T, Liu W, Lu Y, Mills G, Motter T, Weinstein J, Diao L, Wang J, Hong Fan Y, Liu J, Wang K, Todd Auman J, Balu S, Bodenheimer T, Buda E, Neil Hayes D, Hoadley K, Hoyle A, Jefferys S, Jones C, Kimes P, Liu Y, Marron J, Meng S, Mieczkowski P, Mose L, Parker J, Perou C, Prins J, Roach J, Shi Y, Simons J, Singh D, Soloway M, Tan D, Veluvolu U, Walter V, Waring S, Wilkerson M, Wu J, Zhao N, Cherniack A, Hammerman P, Tward A, Sekhar Pedamallu C, Saksena G, Jung J, Ojesina A, Carter S, Zack T, Schumacher S, Beroukhim R, Freeman S, Meyerson M, Cho J, Chin L, Getz G, Noble M, DiCara D, Zhang H, Heiman D, Gehlenborg N, Voet D, Lin P, Frazer S, Stojanov P, Liu Y, Zou L, Kim J, Sougnez C, Gabriel S, Lawrence M, Muzny D, Doddapaneni H, Kovar C, Reid J, Morton D, Han Y, Hale W, Chao H, Chang K, Drummond J, Gibbs R, Kakkar N, Wheeler D, Xi L, Ciriello G, Ladanyi M, Lee W, Ramirez R, Sander C, Shen R, Sinha R, Weinhold N, Taylor B, Arman Aksoy B, Dresdner G, Gao J, Gross B, Jacobsen A, Reva B, Schultz N, Onur Sumer S, Sun Y, Chan T, Morris L, Stuart J, Benz S, Ng S, Benz C, Yau C, Baylin S, Cope L, Danilova L, Herman J, Bootwalla M, Maglinte D, Laird P, Triche T, Weisenberger D, Van Den Berg D, Agrawal N, Bishop J, Boutros P, Bruce J, Averett Byers L, Califano J, Carey T, Chen Z, Cheng H, Chiosea S, Cohen E, Diergaarde B, Marie Egloff A, El-Naggar A, Ferris R, Frederick M, Grandis J, Guo Y, Haddad R, Hammerman P, Harris T, Neil Hayes D, Hui A, Jack Lee J, Lippman S, Liu F, McHugh J, Myers J, Kwok Shing Ng P, Perez-Ordonez B, Pickering C, Prystowsky M, Romkes M, Saleh A, Sartor M, Seethala R, Seiwert T, Si H, Tward A, Van Waes C, Waggott D, Wiznerowicz M, Yarbrough W, Zhang J, Zuo Z, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Yena P, Black A, Bowen J, Frick J, Gastier-Foster J, Harper H, Leraas K, Lichtenberg T, Ramirez N, Wise L, Zmuda E, Baboud J, Jensen M, Kahn A, Pihl T, Pot D, Srinivasan D, Walton J, Wan Y, Burton R, Davidsen T, Demchok J, Eley G, Ferguson M, Mills Shaw K, Ozenberger B, Sheth M, Sofia H, Tarnuzzer R, Wang Z, Yang L, Claude Zenklusen J, Saller C, Tarvin K, Chen C, Bollag R, Weinberger P, Golusiński W, Golusiński P, Ibbs M, Korski K, Mackiewicz A, Suchorska W, Szybiak B, Wiznerowicz M, Burnett K, Curley E, Gardner J, Mallery D, Penny R, Shelton T, Yena P, Beard C, Mitchell C, Sandusky G, Agrawal N, Ahn J, Bishop J, Califano J, Khan Z, Bruce J, Hui A, Irish J, Liu F, Perez-Ordonez B, Waldron J, Boutros P, Waggott D, Myers J, William W, Lippman S, Egea S, Gomez-Fernandez C, Herbert L, Bradford C, Carey T, Chepeha D, Haddad A, Jones T, Komarck C, Malakh M, McHugh J, Moyer J, Nguyen A, Peterson L, Prince M, Rozek L, Sartor M, Taylor E, Walline H, Wolf G, Boice L, Chera B, Funkhouser W, Gulley M, Hackman T, Neil Hayes D, Hayward M, Huang M, Kimryn Rathmell W, Salazar A, Shockley W, Shores C, Thorne L, Weissler M, Wrenn S, Zanation A, Chiosea S, Diergaarde B, Marie Egloff A, Ferris R, Romkes M, Seethala R, Brown B, Guo Y, Pham M, Yarbrough W. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015, 517: 576-582. PMID: 25631445, PMCID: PMC4311405, DOI: 10.1038/nature14129.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellDNA Copy Number VariationsDNA, NeoplasmFemaleGene Expression Regulation, NeoplasticGenome, HumanGenomicsHead and Neck NeoplasmsHumansMaleMolecular Targeted TherapyMutationOncogenesRNA, NeoplasmSignal TransductionSquamous Cell Carcinoma of Head and NeckTranscription FactorsConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaCopy number alterationsMutations of HRASFavorable clinical outcomeFrequent copy number alterationsComprehensive genomic characterizationNumber alterationsFunction TP53 mutationsCancer Genome AtlasSomatic genomic alterationsClinical outcomesLaryngeal tumorsOral cavityFunction alterationsTP53 mutationsCandidate alterationsOncogene PIK3CALoss of TRAF3Novel alterationsCDKN2A inactivationGenome AtlasGenomic alterationsDomain mutations
2014
HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells
Hah JH, Zhao M, Pickering CR, Frederick MJ, Andrews GA, Jasser SA, Fooshee DR, Milas ZL, Galer C, Sano D, William WN, Kim E, Heymach J, Byers LA, Papadimitrakopoulou V, Myers JN. HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells. Head & Neck 2014, 36: 1547-1554. PMID: 24123531, PMCID: PMC4010580, DOI: 10.1002/hed.23499.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCell ProliferationDown-RegulationDrug Resistance, NeoplasmErlotinib HydrochlorideHead and Neck NeoplasmsHumansMiceMolecular Targeted TherapyMutationProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)QuinazolinesSensitivity and SpecificitySignal TransductionSquamous Cell Carcinoma of Head and NeckTransfectionConceptsShort hairpin RNACell linesHRAS expressionErlotinib sensitivityErlotinib-sensitive cell linesErlotinib-resistant cell linesErlotinib resistanceHRAS mutationsNeck squamous cell carcinoma cellsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinibNeck squamous cell carcinoma cell linesSquamous cell carcinoma cellsTyrosine kinase inhibitor erlotinibPanel of headReceptor tyrosine kinase inhibitorsHairpin RNAHNSCC cell linesSquamous cell carcinoma cell linesCell carcinoma cell linesCarcinoma cell linesKinase inhibitor erlotinibTyrosine kinase inhibitorsMutations
2013
FXR silencing in human colon cancer by DNA methylation and KRAS signaling
Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, Liang H, Kopetz S, Powis G, Guo GL. FXR silencing in human colon cancer by DNA methylation and KRAS signaling. AJP Gastrointestinal And Liver Physiology 2013, 306: g48-g58. PMID: 24177031, PMCID: PMC3920083, DOI: 10.1152/ajpgi.00234.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBile Acids and SaltsCarcinogenesisCell Line, TumorColonColonic NeoplasmsColonic PolypsDNA MethylationEpithelial-Mesenchymal TransitionGene SilencingHumansNeoplasm StagingProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReceptors, Cytoplasmic and NuclearSignal TransductionConceptsDNA methylationHuman colon cancerHuman colon cancer progressionMethyl-DNA immunoprecipitationRegulation of FXRFarnesoid X receptorMesenchymal transitionOncogenic signaling cascadesMouse knockout studiesReverse phase protein arrayColon cancer progressionDNA methyltransferase inhibitionFunction of FXRCancer Genome Atlas (TCGA) samplesColon cancer cell linesColon cancer samplesCancer Genome AtlasBisulfite sequencingMethylation patternsKnockout studiesColon cancer developmentSignaling cascadesMethyltransferase inhibitionTumor suppressorPhosphatidylinositol 4Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53
Gadhikar MA, Sciuto MR, Alves MV, Pickering CR, Osman AA, Neskey DM, Zhao M, Fitzgerald AL, Myers JN, Frederick MJ. Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53. Molecular Cancer Therapeutics 2013, 12: 1860-1873. PMID: 23839309, PMCID: PMC3955083, DOI: 10.1158/1535-7163.mct-13-0157.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCell Line, TumorCellular SenescenceCheckpoint Kinase 1Checkpoint Kinase 2CisplatinDNA DamageDrug Resistance, NeoplasmHead and Neck NeoplasmsHumansMitosisMolecular Targeted TherapyMutationProtein Kinase InhibitorsProtein KinasesSignal TransductionThiophenesTumor Suppressor Protein p53UreaConceptsHNSCC cellsCisplatin resistanceAdvanced stage squamous cell carcinomaStage squamous cell carcinomaSquamous cell carcinomaTreatment of HNSCCP53 mutant tumorsLoss of TP53Neck cancer cellsWild-type TP53Multimodality therapyStandard therapyTreatment failureCell carcinomaPreclinical dataHNSCC tumorsTherapeutic advantageTP53 mutationsP53 mutationsTargeted inhibitionPersonalized approachHNSCCP53-deficient cellsKinase inhibitorsSynthetic lethal mannerCoordinated Targeting of the EGFR Signaling Axis by MicroRNA-27a*
Wu X, Bhayani MK, Dodge CT, Nicoloso MS, Chen Y, Yan X, Adachi M, Thomas L, Galer CE, Jiffar T, Pickering CR, Kupferman ME, Myers JN, Calin GA, Lai SY. Coordinated Targeting of the EGFR Signaling Axis by MicroRNA-27a*. Oncotarget 2013, 4: 1388-1398. PMID: 23963114, PMCID: PMC3824521, DOI: 10.18632/oncotarget.1239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCarcinoma, Squamous CellCell Growth ProcessesCell Line, TumorCell SurvivalDown-RegulationErbB ReceptorsHead and Neck NeoplasmsHumansMiceMicroRNAsProto-Oncogene Proteins c-aktRNA, MessengerSignal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsEpidermal growth factor receptorDownregulation of EGFRSolid tumorsTumor growthNeck squamous cell carcinomaMurine orthotopic xenograft modelHNSCC cell viabilityOral cavity cancerMultiple HNSCC cell linesSquamous cell carcinomaStar strandNovel therapeutic optionsNovel miRNAsMultiple solid tumorsOrthotopic xenograft modelOverexpression of EGFRCoordinated regulationHNSCC cell linesCoordinated targetingGrowth factor receptorComplex regulationDirect intratumoral injectionPathway componentsInducible expressionSignaling Axis
2011
Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples
Frederick MJ, VanMeter AJ, Gadhikar MA, Henderson YC, Yao H, Pickering CC, Williams MD, El-Naggar AK, Sandulache V, Tarco E, Myers JN, Clayman GL, Liotta LA, Petricoin EF, Calvert VS, Fodale V, Wang J, Weber RS. Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples. American Journal Of Pathology 2011, 178: 548-571. PMID: 21281788, PMCID: PMC3070553, DOI: 10.1016/j.ajpath.2010.10.044.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBlotting, WesternCarcinoma, Squamous CellCell Line, TumorCluster AnalysisFemaleHead and Neck NeoplasmsHumansImmunohistochemistryMaleMucous MembraneNeoplasm ProteinsPhosphoproteinsPhosphorylationProtein Array AnalysisProtein Kinase CProteomicsReproducibility of ResultsSignal TransductionConceptsReverse-phase protein microarrayNeck squamous cell carcinomaSquamous cell carcinomaEukaryotic translation initiation factor 4ETranslation initiation factor 4ECell carcinomaInitiation factor 4ESmall molecule inhibitorsSerine 345Phosphoproteomic analysisChk-2Protein kinaseSignaling pathwaysElevated analytesPatient-specific differencesLung cancerBiopsy specimensPromising new strategyProtein microarraysTumor typesTheranostic testsEnd pointPatient samplesTumorsPersonalized therapy
2010
DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions
Fordyce C, Fessenden T, Pickering C, Jung J, Singla V, Berman H, Tlsty T. DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions. Cancer Prevention Research 2010, 3: 190-201. PMID: 20028875, PMCID: PMC2954106, DOI: 10.1158/1940-6207.capr-09-0229.Peer-Reviewed Original ResearchMeSH KeywordsActivinsAtaxia Telangiectasia Mutated ProteinsBlotting, WesternBreast NeoplasmsCarcinoma in SituCarcinoma, Ductal, BreastCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Cyclooxygenase 2DNA DamageDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryNeoplasm ProteinsOligonucleotide Array Sequence AnalysisPrecancerous ConditionsProtein Serine-Threonine KinasesRetinoblastoma ProteinReverse Transcriptase Polymerase Chain ReactionSignal TransductionTelomereTelomeric Repeat Binding Protein 2Tumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsCOX-2 expressionCyclooxygenase-2Activin AEpithelial cellsHigh COX-2 expressionPoor clinical outcomeCOX-2 inhibitionCOX-2 inhibitorsTumor-promoting phenotypeSynthesis of prostaglandinsDNA damageDependent inductionVariant human mammary epithelial cellsBreast epithelial cellsHuman mammary epithelial cellsGastrointestinal complicationsSystemic complicationsClinical outcomesDuctal carcinomaCell cycle arrestSitu lesionsChemopreventative agentMammary epithelial cellsCancer metastasisPremalignant cells
2006
p16INK4a Modulates p53 in Primary Human Mammary Epithelial Cells
Zhang J, Pickering CR, Holst CR, Gauthier ML, Tlsty TD. p16INK4a Modulates p53 in Primary Human Mammary Epithelial Cells. Cancer Research 2006, 66: 10325-10331. PMID: 17079452, DOI: 10.1158/0008-5472.can-06-1594.Peer-Reviewed Original ResearchConceptsPrimary human mammary epithelial cellsHuman mammary epithelial cellsMammary epithelial cellsCell type-specific regulationTumor suppressor geneStabilization of p53Epithelial cellsP53 protein levelsE2F/Gene activityDownstream targetsCellular responsesSuppressor geneProteolytic degradationProtein levelsP53 proteinP16 proteinP53ProteinReduced levelsP53 statusPathwayCellsGenesRegulation