2022
Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV Exposure†
Garcia‐Ruiz A, Kornacker K, Brash DE. Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV Exposure†. Photochemistry And Photobiology 2022, 98: 987-997. PMID: 35944237, PMCID: PMC9802031, DOI: 10.1111/php.13683.Peer-Reviewed Original ResearchConceptsCyclobutane pyrimidine dimersGenomic averageSequence motifsHigh-throughput DNA sequencing methodsETS family transcription factorsNucleotide resolution analysisRNA processing genesNeonatal human epidermal keratinocytesDNA sequencing methodsTranscription factorsCpG islandsSites hundredsCell physiologyProcessing genesPromoter regionCell deathDNA damageSequencing methodsBiological importanceHuman epidermal keratinocytesPyrimidine dimersGenesMotifEpidermal keratinocytesMelanocytes
2016
Chemical excitation of electrons: A dark path to melanoma
Premi S, Brash DE. Chemical excitation of electrons: A dark path to melanoma. DNA Repair 2016, 44: 169-177. PMID: 27262612, PMCID: PMC4958542, DOI: 10.1016/j.dnarep.2016.05.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2006
Keratinocyte Apoptosis in Epidermal Development and Disease
Raj D, Brash DE, Grossman D. Keratinocyte Apoptosis in Epidermal Development and Disease. Journal Of Investigative Dermatology 2006, 126: 243-257. PMID: 16418733, PMCID: PMC2291295, DOI: 10.1038/sj.jid.5700008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEpidermal developmentNormal developmental programPre-malignant cellsDevelopmental programApoptosis controlMolecular mechanismsKeratinocyte apoptosisDysfunctional apoptosisKC apoptosisApoptosisCritical roleComplex roleNew insightsCorneum formationMouse modelCarcinogenesisSkin carcinogenesisPathwayRoleProliferationCells
2005
Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis
Chaturvedi V, Sitailo LA, Qin JZ, Bodner B, Denning MF, Curry J, Zhang W, Brash D, Nickoloff BJ. Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis. Oncogene 2005, 24: 5299-5312. PMID: 15940268, DOI: 10.1038/sj.onc.1208650.Peer-Reviewed Original ResearchConceptsMouse modelP53 levelsP53 siRNAHuman keratinocytesMcl-1Skin cancer developmentKnockout mouse modelP53 tumor suppressor geneCultured human keratinocytesBcl-xL antiapoptotic proteinBcl-xL levelsCommon causeParadoxical responseSkin cancerAccelerated eliminationUltraviolet light exposureWild-type p53Cancer developmentTumor suppressor geneUV-induced DNA damageEpidermal responseE2F-1 levelsPrimary culturesSiRNA-based approachAbnormal cellsColonization of adjacent stem cell compartments by mutant keratinocytes
Brash DE, Zhang W, Grossman D, Takeuchi S. Colonization of adjacent stem cell compartments by mutant keratinocytes. Seminars In Cancer Biology 2005, 15: 97-102. PMID: 15652454, DOI: 10.1016/j.semcancer.2004.08.006.ChaptersMeSH KeywordsAnimalsApoptosisKeratinocytesMutagenesisSkin NeoplasmsStem CellsTumor Suppressor Protein p53Ultraviolet RaysConceptsStem cell compartmentMutant stem cellsCell compartmentStem cellsDNA-damaged cellsNon-mutational mechanismsMutant cellsAdditional genesClonal expansionSelection pressureP53 mutant cellsUVB-induced apoptosisMutant keratinocytesCancer developmentCompartmentsCellsAbsence of escapeKeratinocyte clonesAdditional territoryClinical phenotypeAdjacent compartmentsGenesMechanismClonesPhenotype
2004
UVB-induced apoptosis drives clonal expansion during skin tumor development
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, Brash DE, Grossman D. UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2004, 26: 249-257. PMID: 15498793, PMCID: PMC2292404, DOI: 10.1093/carcin/bgh300.Peer-Reviewed Original Research
2003
Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice
Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nature Cell Biology 2003, 5: 655-660. PMID: 12833065, DOI: 10.1038/ncb1001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell SurvivalCell Transformation, NeoplasticCells, CulturedDNA DamageDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorFemaleFibroblastsGene Expression Regulation, NeoplasticGenes, SuppressorKeratinocytesMaleMiceMice, KnockoutMutationSex RatioSkin NeoplasmsTranscription FactorsTumor Suppressor Protein p53Ultraviolet RaysConceptsUVB-induced apoptosisEarly-onset tumorsDouble knockout miceTrp53-deficient miceKnockout miceCancer sensitivityUVB exposureGenetic abnormalitiesMiceKeratinocyte apoptosisProtective mechanismApoptosis defectsApoptosis resistanceApoptosisDouble knockoutApoptosis pathwayE2F1 transcription factorE2F1 functionsPrimary fibroblastsE2F1Trp53S phase
2001
Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations
Zhang W, Remenyik E, Zelterman D, Brash D, Wikonkal N. Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 13948-13953. PMID: 11707578, PMCID: PMC61147, DOI: 10.1073/pnas.241353198.Peer-Reviewed Original ResearchTransgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53
Grossman D, Kim P, Blanc-Brude O, Brash D, Tognin S, Marchisio P, Altieri D. Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53. Journal Of Clinical Investigation 2001, 108: 991-999. PMID: 11581300, PMCID: PMC200956, DOI: 10.1172/jci13345.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisChromosomal Proteins, Non-HistoneGene ExpressionHumansInhibitor of Apoptosis ProteinsKeratin-14KeratinocytesKeratinsMiceMice, KnockoutMice, TransgenicMicrotubule-Associated ProteinsNeoplasm ProteinsPhenotypePromoter Regions, GeneticSkinSurvivinTumor Suppressor Protein p53Ultraviolet Rays
2000
Regulation of TNFα production and release in human and mouse keratinocytes and mouse skin after UV‐B irradiation
Yarosh D, Both D, Kibitel J, Anderson C, Elmets C, Brash D, Brown D. Regulation of TNFα production and release in human and mouse keratinocytes and mouse skin after UV‐B irradiation. Photodermatology Photoimmunology & Photomedicine 2000, 16: 263-270. PMID: 11132130, DOI: 10.1034/j.1600-0781.2000.160606.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell LineCell MembraneEnzyme-Linked Immunosorbent AssayGene Expression RegulationGenes, fosGenes, p53HomozygoteHumansInterleukin-1KeratinocytesMaleMiceMice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesRadiation DosageReceptors, Tumor Necrosis FactorReverse Transcriptase Polymerase Chain ReactionSignal TransductionSirolimusSkinTranscription Factor AP-1Tumor Necrosis Factor-alphaUltraviolet RaysConceptsP53 knockout miceKnockout miceMembrane-bound TNFalphaHomozygous p53 knockout miceC-Fos signalingWild-type miceGene knockout miceRelease of TNFalphaTNFalpha gene expressionAP-1Cultured human keratinocytesImmunosuppressive responseCell culture supernatantsAP-1 transcription factorCultured epidermal cellsIL-1alphaCytokine TNFalphaTNFα productionType micePrimary cytokineTNFalpha inductionTNFalphaBasal levelsMouse skinMice
1999
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine
Liu M, Wikonkal N, Brash D. Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 1999, 20: 1869-1872. PMID: 10469636, DOI: 10.1093/carcin/20.9.1869.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAnticarcinogenic AgentsAntioxidantsCell CycleCell LineChromansCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsFibroblastsFree Radical ScavengersG1 PhaseGene Expression RegulationGene Expression Regulation, NeoplasticGenes, p16GlutathioneHumansKeratinocytesMiceModels, BiologicalNeoplasm ProteinsPapillomaSkin NeoplasmsTumor Cells, CulturedTumor Suppressor Protein p53ConceptsCyclin-dependent kinase inhibitorNovel molecular basisCell cycle transitionKinase inhibitorsDNA replicationDNA repairCellular differentiationMolecular basisG1 prolongationGene expressionAntioxidant N-acetylcysteineN-acetylcysteineIntracellular glutathione levelsArrestAgent N-acetylcysteineInductionInhibitorsGlutathione levelsCyclinChemopreventive agentsChemopreventive activityDifferentiationUsual mechanismP53ReplicationUltraviolet Radiation Induced Signature Mutations in Photocarcinogenesis
Wikonkal N, Brash D. Ultraviolet Radiation Induced Signature Mutations in Photocarcinogenesis. Journal Of Investigative Dermatology Symposium Proceedings 1999, 4: 6-10. PMID: 10537000, DOI: 10.1038/sj.jidsp.5640173.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSignature mutationsSkin cancerNon-melanoma skin cancerUV-signature mutationsClinical dataSubstantial burdenSkin carcinogenesisMurine epidermisNormal individualsNormal humansCancerCancer developmentTumor suppressor geneClonal expansionTumor promoterTP53Suppressor geneGenetic eventsMutationsCellsUV Induces p21WAF1/CIP1 Protein in Keratinocytes Without p53
Liu M, Wikonkal N, Brash D. UV Induces p21WAF1/CIP1 Protein in Keratinocytes Without p53. Journal Of Investigative Dermatology 1999, 113: 283-284. PMID: 10469320, DOI: 10.1046/j.1523-1747.1999.00657.x.Peer-Reviewed Original Research
1996
Frequent clones of p53-mutated keratinocytes in normal human skin
Jonason A, Kunala S, Price G, Restifo R, Spinelli H, Persing J, Leffell D, Tarone R, Brash D. Frequent clones of p53-mutated keratinocytes in normal human skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 14025-14029. PMID: 8943054, PMCID: PMC19488, DOI: 10.1073/pnas.93.24.14025.Peer-Reviewed Original ResearchConceptsP53-mutated keratinocytesNormal individualsSun-shielded skinSun-exposed skinNormal human skinHuman skinWhole-mount preparationsP53-mutated cellsCancer predictsDermal-epidermal junctionSubstantial burdenFrequent clonesClonal expansionHair folliclesGenetic hitsTumor promoterSkinKeratinocytesCells