2009
Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia
Klein AM, Brash DE, Jones PH, Simons BD. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 270-275. PMID: 20018764, PMCID: PMC2806764, DOI: 10.1073/pnas.0909738107.Peer-Reviewed Original ResearchConceptsP53 mutationsNonmelanoma skin cancer incidenceSame cumulative doseSkin cancer incidenceUVB radiationUV-irradiated epidermisP53 tumor suppressor geneP53-mutant clonesCumulative doseCancer incidenceP53 mutant cellsHigh-intensity exposureMurine epidermisPreneoplastic clonesTumor suppressor geneProgenitor cellsExposure resultsPrecancerous cellsPreneoplastic cellsHuman epidermisB radiationClones of cellsInfluence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA
Rochette PJ, Lacoste S, Therrien JP, Bastien N, Brash DE, Drouin R. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2009, 665: 7-13. PMID: 19427505, DOI: 10.1016/j.mrfmmm.2009.02.008.Peer-Reviewed Original ResearchConceptsLigation-mediated PCRX chromosomeFMR1 geneGenomic DNAInactive X chromosomeDimer formationCyclobutane pyrimidine dimer formationTumor suppressor genePyrimidine dimer formationConstitutive methylationCytosine methylationMethylated cytosineUnmethylated cytosinesSuppressor geneP53 tumor suppressor geneGenesMethylationCPD formationChromosomesCytosineDNAMutationsSunlight-induced mutationsDipyrimidine sitesPGK1
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 cellsPTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer
Asplund A, Gustafsson AC, Wikonkal NM, Sela A, Leffell DJ, Kidd K, Lundeberg J, Brash DE, Pontén F. PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer. British Journal Of Dermatology 2005, 152: 868-873. PMID: 15888139, DOI: 10.1111/j.1365-2133.2005.06464.x.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Basal CellCarcinoma, Squamous CellCodonGenetic Predisposition to DiseaseGenotypeHair ColorHumansLoss of HeterozygosityNeoplasm ProteinsPatched ReceptorsPatched-1 ReceptorPilot ProjectsPolymerase Chain ReactionPolymorphism, Single NucleotideReceptors, Cell SurfaceSkin NeoplasmsSkin PigmentationConceptsPro/Pro genotypeNonmelanoma skin cancerBasal cell carcinomaPTCH tumor suppressor geneSquamous cell carcinomaAllele frequency variationAllelic loss studiesTumor suppressor genePro genotypeSingle nucleotide polymorphismsAllelic lossGenomic DNANonrandom lossSuppressor geneCell carcinomaSwedish patientsEpithelial cell cancersLight pigmentationSkin cancerNucleotide polymorphismsMultiple basal cell carcinomasPro/LeuHuman populationPTCH geneAllele frequencies
1999
Ultraviolet 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 eventsMutationsCells
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
1996
Sunlight 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
1991
A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma.
Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Pontén J. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 10124-10128. PMID: 1946433, PMCID: PMC52880, DOI: 10.1073/pnas.88.22.10124.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaCell carcinomaP53 mutationsMajor epidemiologic risk factorsUV-induced p53 mutationsInvasive squamous cell carcinomaEpidemiologic risk factorsUV-specific mutationsP53 tumor suppressor geneInternal malignancySwedish patientsRisk factorsSkin cancerTumor progressionTT double-base changesTumor suppressor geneCarcinomaHuman cancersCancerDipyrimidine sitesSuppressor geneT substitutionSkinMutationsPatients