2008
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15034-15039. PMID: 18815380, PMCID: PMC2567488, DOI: 10.1073/pnas.0802211105.Peer-Reviewed Original ResearchConceptsNormal stem cellsStem cellsClonal expansionCell replicationMutant cellsNormal cell replicationMutant clonesProliferative advantageDorsal epidermisCell mutationTissue architectureClonesClone growthBiological observationsCell killingApoptosis rateReplicationMutationsGrowth rateCellsGrowthNormal territoriesApoptosisExponential growth modelImportant stepProgressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL
Rochette PJ, Brash DE. Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL. Mechanisms Of Ageing And Development 2008, 129: 207-214. PMID: 18262222, PMCID: PMC2652169, DOI: 10.1016/j.mad.2007.12.007.Peer-Reviewed Original ResearchConceptsAnti-apoptotic protein Bcl-xLBcl-xLProtein Bcl-xLLevels of p53Pro-apoptotic protein BaxApoptosis reductionAnti-apoptotic proteinsPro-apoptotic BaxNormal balanceAnti-apoptotic Bcl-xLUV-induced apoptosisOld cellsApoptosis resistanceProgressive disruptionSenescent cellsApoptosisBaxProtein BaxHuman diploid fibroblastsCellsYoung cellsDiploid fibroblastsGenotoxic stressLevels
2007
Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling
Knezevic D, Zhang W, Rochette PJ, Brash DE. Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 11286-11291. PMID: 17586682, PMCID: PMC2040891, DOI: 10.1073/pnas.0701318104.Peer-Reviewed Original Research
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.ChaptersConceptsStem 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
Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin
Takeuchi S, Zhang W, Wakamatsu K, Ito S, Hearing VJ, Kraemer KH, Brash DE. Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 15076-15081. PMID: 15477596, PMCID: PMC524044, DOI: 10.1073/pnas.0403994101.Peer-Reviewed Original ResearchConceptsYellow miceTerminal deoxynucleotidyltransferase-mediated dUTP nickTUNEL-positive cellsActive caspase-3Sunburn cellsPositive cellsBlack miceSkin cancerCongenic miceMurine skinDUTP nickDNA strand breaksMiceEpidermal sheetsHair folliclesAbility of melaninCaspase-3Sensitivity of individualsApoptosisLesionsUVA radiationRed hairCell deathHair shaftSunlight UV radiationUVB-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 ResearchRole of E2F1 in Apoptosis: A case Study in Feedback Loops
Knezevic D, Brash DE. Role of E2F1 in Apoptosis: A case Study in Feedback Loops. Cell Cycle 2004, 3: 727-730. PMID: 15107604, DOI: 10.4161/cc.3.6.907.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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
2002
New careers for antioxidants
Brash DE, Havre PA. New careers for antioxidants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 13969-13971. PMID: 12391310, PMCID: PMC137820, DOI: 10.1073/pnas.232574399.Commentaries, Editorials and LettersTransformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine.
Havre PA, O'Reilly S, McCormick JJ, Brash DE. Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine. Cancer Research 2002, 62: 1443-9. PMID: 11888918.Peer-Reviewed Original Research
2001
The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes
Brash D, Wikonkal N, Remenyik E, van der Horst G, Friedberg E, Cheo D, van Steeg H, Westerman A, van Kranen H. The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes. Journal Of Investigative Dermatology 2001, 117: 1234-1240. PMID: 11710938, DOI: 10.1046/j.0022-202x.2001.01554.x.Peer-Reviewed Original ResearchConceptsDNA photoproductsDNA damage signalsUnrepaired DNA lesionsCell formationSpecific genome regionsTumor suppressor proteinCsb-/- miceUltraviolet-induced apoptosisNucleotide excision repair genesApoptosis signal pathwayExcision repair genesActive genesMutant cellsGenome regionsDNA repairSuppressor proteinDamage signalsMDM2 regulationWild typeDNA lesionsPrevents cellsHomozygous inactivationGenesRepair genesDNA signalsTransgenic 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
1998
Antioxidant action via p53-mediated apoptosis.
Liu M, Pelling JC, Ju J, Chu E, Brash DE. Antioxidant action via p53-mediated apoptosis. Cancer Research 1998, 58: 1723-9. PMID: 9563490.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsApoptosisBlotting, NorthernBlotting, WesternButhionine SulfoximineCells, CulturedDimercaprolDose-Response Relationship, DrugGene Expression Regulation, NeoplasticGlutathioneMiceOxidation-ReductionPyrrolidonecarboxylic AcidSulfhydryl CompoundsThiazolesThiazolidinesTumor Cells, CulturedTumor Suppressor Protein p53Vitamin EConceptsP53 inductionCellular redox potentialP53-dependent apoptosisNormal cellsP53-mediated apoptosisTumor suppressor geneP53 mRNA translationCellular thiol levelsMRNA translationRedox sensorProtein stabilitySuppressor geneP53 tumor suppressor geneNontoxic antioxidantsApoptosisCell linesSulfur-containing antioxidantsBiological effectsPrimary culturesElevated p53 expressionCellsInductionN-acetylcysteineGlutathione levelsRedox potential
1997
Sunlight and the onset of skin cancer
Brash D. Sunlight and the onset of skin cancer. Trends In Genetics 1997, 13: 410-414. PMID: 9351343, DOI: 10.1016/s0168-9525(97)01246-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1996
Cellular proofreading
Brash D. Cellular proofreading. Nature Medicine 1996, 2: 525-526. PMID: 8616708, DOI: 10.1038/nm0596-525.Commentaries, Editorials and LettersTumor Suppressor Gene Mutations and Photocarcinogenesis
Ziegler A, Jonason A, Simon J, Leffell D, Brash DE. Tumor Suppressor Gene Mutations and Photocarcinogenesis. Photochemistry And Photobiology 1996, 63: 432-435. PMID: 8934758, DOI: 10.1111/j.1751-1097.1996.tb03064.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion.
Brash DE, Ziegler A, Jonason AS, Simon JA, Kunala S, Leffell DJ. Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion. Journal Of Investigative Dermatology Symposium Proceedings 1996, 1: 136-42. PMID: 9627707.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSquamous cell carcinomaCell carcinomaActinic keratosisBasal cell carcinomaHuman skin cancerP53 tumor suppressor geneP53-mutated cellsSunburn cellsApoptotic keratinocytesSkin cancerP53 mutationsNormal skinTumor initiatorTumor promotionFunction of p53Cellular proofreadingTumor suppressor geneCarcinomaMouse skinClonal expansionP53 geneCarcinogenic DNA lesionsP53 allelePrecancerous cellsSunlight exposure
1994
Sunburn and p53 in the onset of skin cancer
Ziegler A, Jonason A, Leffellt D, Simon J, Sharma H, Kimmelman J, Remington L, Jacks T, Brash D. Sunburn and p53 in the onset of skin cancer. Nature 1994, 372: 773-776. PMID: 7997263, DOI: 10.1038/372773a0.Peer-Reviewed Original ResearchConceptsActinic keratosisP53 mutationsSquamous cell carcinomaP53 tumor suppressor geneP53-mutated cellsCell carcinomaApoptotic keratinocytesSkin cancerTumor initiatorTumor suppressor geneMouse skinClonal expansionPrecancerous cellsTumor promoterCarcinomaSkinTissue responseP53SunburnCell differentiationDNA damageAberrant cell differentiationCellsResponseKeratosis