2006
Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification
Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R. Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification. Journal Of Investigative Dermatology 2006, 126: 2257-2271. PMID: 16810302, DOI: 10.1038/sj.jid.5700386.Peer-Reviewed Original ResearchConceptsX chromosome-linked geneSpecific gene expressionTranscription initiation siteSpecific promoter regionsMelanoma cellsGTPase mutantsEpigenetic modificationsSmall GTPaseDNA methylationVesicular transportRab33AGene expressionPromoter regionMelanosomal proteinsInitiation siteNormal melanocytesAberrant downregulationGenesEarly eventsAberrant processesMelanocytesExpressionGTPaseImportant roleNormal process
2004
Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantage
2002
Signal Transduction Abnormalities as Therapeutic Targets
Halaban R, von Willebrand M. Signal Transduction Abnormalities as Therapeutic Targets. Current Clinical Oncology 2002, 287-323. DOI: 10.1007/978-1-59259-159-6_11.Peer-Reviewed Original ResearchGrowth factor-mediated signalingNormal melanocytesChronic myelogenous leukemiaSignal transduction targetsSpecific kinase inhibitorsCell cycle regulatorsCell cycle progressionAutonomous cell proliferationEpidermal growth factor receptor familyEffective tumor suppressorSignal transduction abnormalitiesGrowth factor receptor familyMelanoma cellsTyrosine kinase receptorsFactor receptor familyReceptor kinaseEnvironmental cuesRegulatory proteinsActive Abl kinasesCycle regulatorsCycle progressionTumor suppressorAbl kinaseKinase receptorsOncogenic mutations
2000
Translation Rate of Human Tyrosinase Determines ItsN-Linked Glycosylation Level*
Újvári A, Aron R, Eisenhaure T, Cheng E, Parag H, Smicun Y, Halaban R, Hebert D. Translation Rate of Human Tyrosinase Determines ItsN-Linked Glycosylation Level*. Journal Of Biological Chemistry 2000, 276: 5924-5931. PMID: 11069924, DOI: 10.1074/jbc.m009203200.Peer-Reviewed Original ResearchConceptsTranslation rateCell-free systemProtein translation ratesType I membrane glycoproteinsNormal melanocytesHuman tyrosinaseSemi-permeabilized cellsMelanoma cellsUbiquitin-proteasomal pathwayRate of translationSite-directed mutagenesisWild-type tyrosinaseProtein synthesis inhibitor cycloheximideInefficient glycosylationGlycosylation efficiencyAberrant retentionProtein translationCotranslational eventsConsensus sitesCore glycanDegradative fateProtein doubletEndoplasmic reticulumMaturation eventsAmelanotic melanoma cellsDeregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells
Halaban R, Cheng E, Smicun Y, Germino J. Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells. Journal Of Experimental Medicine 2000, 191: 1005-1016. PMID: 10727462, PMCID: PMC2193116, DOI: 10.1084/jem.191.6.1005.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell DivisionCells, CulturedCellular SenescenceCulture Media, ConditionedCyclin-Dependent KinasesCyclinsDNA-Binding ProteinsDown-RegulationDrosophila ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorE2F4 Transcription FactorE2F5 Transcription FactorE2F6 Transcription FactorEnzyme InhibitorsFlavonoidsHumansMelanocytesMelanomaPhosphorylationPiperidinesProtein BindingRetinoblastoma-Binding Protein 1Trans-ActivatorsTranscription Factor DP1Transcription FactorsTumor Cells, CulturedConceptsExternal growth factorsE2F DNAPocket proteinsCyclin-dependent kinase 4Normal melanocytesTranscriptional activityRetinoblastoma tumor suppressor proteinMelanoma cellsMalignant human melanocytesE2F transcription factorsE2F family membersE2F transcriptional activityTumor suppressor proteinGel shift analysisCell cycle progressionForm of pRBGrowth factorContinuous high expressionE2F activityOnly family memberTranscription factorsProtein DNASuppressor proteinFamily membersMolecular basis
1999
Melanoma Cell Autonomous Growth: The Rb/E2F Pathway
Halaban R. Melanoma Cell Autonomous Growth: The Rb/E2F Pathway. Cancer And Metastasis Reviews 1999, 18: 333-343. PMID: 10721488, DOI: 10.1023/a:1006396104073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsHumansMelanocytesMelanomaPhosphorylationRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Signal TransductionTranscription Factor DP1Transcription FactorsConceptsPocket proteinsExternal growth factorsNormal melanocytesE2F activityTarget genesRb/E2F pathwayE2F transcription factorsCell surface receptor stimulationMelanoma cellsCell-autonomous growthTumor suppressor proteinClass of enzymesCyclin-dependent kinasesInactivation of pRbConstitutive high expressionGrowth factorCell cycle progressionSurface receptor stimulationMetastatic melanoma cellsRetinoblastoma familySuppressive complexE2F pathwayPositive regulatorTranscription factorsMouse melanocytes
1998
Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1
Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene 1998, 16: 2489-2501. PMID: 9627115, DOI: 10.1038/sj.onc.1201773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell SurvivalCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorGene Expression RegulationHumansMelanocytesMiceMice, NudeMutagenesisProtein BiosynthesisRecombinant Fusion ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Tetradecanoylphorbol AcetateTranscription Factor DP1Transcription FactorsConceptsP21WAF1/CIP1Cell cycle progressionMouse melanocytesTarget genesCycle progressionRetinoblastoma tumor suppressor proteinE2F-mediated transactivationCell cycle constraintsTumor suppressor proteinRole of E2F1Deletion of p16INK4AFree E2FExpression of RbGene disruptionSuppressor proteinEctopic expressionHallmark of melanomaTetradecanoyl phorbol 13Loss of p16INK4aConstitutive expressionMelanoma cell linesCell deathNormal melanocytesIndependent growthMelanocyte growth
1997
Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein.
Miglarese M, Halaban R, Gibson N. Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein. Molecular Cancer Research 1997, 8: 1199-210. PMID: 9372243.Peer-Reviewed Original ResearchConceptsFGF-2 promoterMurine c-MybSK-MEL-2 human melanoma cellsC-MybFunctional DNA-binding domainHuman melanoma cellsDNA-binding domainMelanoma cellsAutocrine growthPutative MybC-myb mRNATranscription factorsEctopic expressionPromoter regionFibroblast growth factorBasic fibroblast growth factorMelanoma cell linesReporter plasmidNormal melanocytesFibroblast growth factor-2 expressionPromoterGrowth factor 2 expressionMYBFGF-2 proteinCell linesSuppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases
Yayon A, Ma Y, Safran M, Klagsbrun M, Halaban R. Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases. Oncogene 1997, 14: 2999-3009. PMID: 9223663, DOI: 10.1038/sj.onc.1201159.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCell DivisionCell Line, TransformedFibroblast Growth Factor 2FibroblastsFilaggrin ProteinsGenes, DominantHumansMelanomaMicePhenotypeProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorRecombinant ProteinsSrc Homology DomainsTumor Cells, CulturedConceptsSrc family kinasesFGF receptor 1FGF receptorsTyrosyl-phosphorylated proteinsHuman melanoma cellsMelanoma cellsImmune kinase assayIntracellular kinase domainDominant negative mutantActivated FGF receptorCell proliferationMetastatic melanoma cellsMelanoma tumor progressionGrowth factorTransmembrane domainKinase assaysSrc familyKinase domainDownstream targetsReceptor 1Fibroblast growth factorBasic fibroblast growth factorGrowth advantageNormal melanocytesAutocrine activationAberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells
Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert D. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6210-6215. PMID: 9177196, PMCID: PMC21028, DOI: 10.1073/pnas.94.12.6210.Peer-Reviewed Original ResearchMeSH KeywordsAdultCalcium-Binding ProteinsCalnexinCalreticulinCell DifferentiationCells, CulturedCoculture TechniquesEndoplasmic ReticulumEnzyme PrecursorsHumansInfant, NewbornKineticsMelanocytesMelanomaMolecular ChaperonesMolecular WeightMonophenol MonooxygenasePhenotypeRibonucleoproteinsSkin NeoplasmsTime FactorsTumor Cells, CulturedConceptsEndoplasmic reticulumNormal melanocytesER chaperone calnexinMelanin synthesisMalignant melanocytesMelanoma cellsChaperone bindingAberrant retentionChaperone calnexinGolgi compartmentSubcellular localizationAmelanotic melanoma cell lineKey enzymeMelanoma cell linesMaturation of tyrosinaseAmelanotic melanoma cellsKinetics of synthesisInhibitor sensitivityDedifferentiated phenotypeProteolytic degradationCell linesProteasome inhibitorsEnzymeProteasomeImmature forms
1993
KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells.
Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S, Halaban R. KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. Oncogene 1993, 8: 2221-9. PMID: 7687762.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionHematopoietic Cell Growth FactorsHumansMelanomaMolecular Sequence DataNeoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-kitRNA, MessengerRNA, NeoplasmStem Cell FactorTumor Cells, CulturedConceptsMast cell growth factorMelanoma cell linesNormal melanocyte developmentMelanoma cellsAberrant signal transductionMetastatic melanoma cell linesCell linesActivation of KITMelanocyte developmentSignal transductionKIT proto-oncogeneKinase activationKIT mRNAKit ligandNormal melanocytesProto-oncogeneKIT kinaseCell growth factorBiological responsesGrowth factorHuman melanomaMelanocytesCellsKIT expressionNeoplastic melanocytesMolecular correlates in the progression of normal melanocytes to melanomas.
Halaban R. Molecular correlates in the progression of normal melanocytes to melanomas. Seminars In Cancer Biology 1993, 4: 171-81. PMID: 8318693.Peer-Reviewed Original ResearchConceptsMelanoma suppressor geneBasic fibroblast growth factorSuppressor geneMolecular basisGrowth factor autonomyTumor suppressor geneGene activationSpecific genesChromosome 1Intracellular loopFibroblast growth factorInappropriate expressionGrowth controlGenesGrowth advantageNormal melanocytesMalignant phenotypeDifferentiated functionsAberrant expressionAutocrine growthMalignant progressionMolecular correlatesGrowth factorMelanocytesInactivationHuman Melanoma Cells but Not Normal Melanocytes Express Vascular Endothelial Growth Factor Receptors
Gitaygoren H, Halaban R, Neufeld G. Human Melanoma Cells but Not Normal Melanocytes Express Vascular Endothelial Growth Factor Receptors. Biochemical And Biophysical Research Communications 1993, 190: 702-709. PMID: 8439321, DOI: 10.1006/bbrc.1993.1106.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCross-Linking ReagentsEndothelial Growth FactorsHeparinHumansIn Vitro TechniquesLymphokinesMelanocytesMelanomaProtein-Tyrosine KinasesReceptors, MitogenReceptors, Vascular Endothelial Growth FactorRecombinant ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsVascular endothelial growth factorHuman melanoma cellsMelanoma cellsMalignant transformationVEGF receptorsVascular endothelial growth factor receptorEndothelial growth factor receptorNormal melanocytesEndothelial growth factorGrowth factor receptorMelanoma cell linesHeparin-like moleculesAngiogenic factorsEndothelial cellsSpecific mitogenAberrant expressionGrowth factorFactor receptorLigand/receptor interactionsReceptorsMalignant melanocytesRadioactive ligandExogenous heparinPossible involvementReceptor interactionGrowth Regulation in Normal and Malignant Melanocytes
Halaban R. Growth Regulation in Normal and Malignant Melanocytes. Recent Results In Cancer Research 1993, 128: 133-150. PMID: 8356315, DOI: 10.1007/978-3-642-84881-0_10.Peer-Reviewed Original ResearchConceptsNormal human melanocytesHuman melanocytesSignal transduction pathwaysGrowth factorMalignant melanocytesGrowth factors/receptorsTransduction pathwaysGrowth regulationConstitutive activationBiochemical basisBiochemical eventsNormal melanocytesGrowth phaseRadial growth phaseMalignant stateMelanocytesMelanoma cellsNormal counterpartsPreneoplastic cellsReceptor activityInappropriate productionCellsMetastatic melanoma lesionsActivationReceptorsmet and HGF-SF in normal melanocytes and melanoma cells.
Halaban R, Rubin J, White W. met and HGF-SF in normal melanocytes and melanoma cells. 1993, 65: 329-39. PMID: 8380740.Peer-Reviewed Original ResearchConceptsHGF-SFFactor-dependent cellsMelanoma cellsNormal human melanocytesSignal transductionMouse melanocytesTumorigenic phenotypeHuman melanocytesHuman melanoma cellsNormal melanocytesAutocrine loopMelanocytesHuman melanomaMalignant conversionMelanin contentTyrosinase activityEctopic sitesCellsSynergistic factorExpressionBFGFERK2TransductionPhosphorylationProtein
1992
Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes
Halaban R, Fan B, Ahn J, Funasaka Y, Gitay-Goren H, Neufeld G. Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes. Journal Of Immunotherapy 1992, 12: 154-161. PMID: 1445804, DOI: 10.1097/00002371-199210000-00002.Peer-Reviewed Original ResearchConceptsMast cell growth factorReceptor tyrosine kinasesFibroblast growth factorTyrosine kinaseTyrosyl-phosphorylated proteinsExpression of pigmentationTransmembrane receptor tyrosine kinaseHepatocyte growth factorGrowth factorGrowth factor/receptor systemsHuman melanocyte proliferationBasic FGFMelanoma cellsProtein tyrosineReceptor kinasePigment cellsBasic fibroblast growth factorFGF receptorsKinaseHuman melanoma cellsNormal melanocytesKIT kinaseMalignant phenotypeMelanocyte proliferationCell growth factor
1991
Proliferation and malignant transformation of melanocytes.
Halaban R, Moellmann G. Proliferation and malignant transformation of melanocytes. Critical Reviews™ In Oncogenesis 1991, 2: 247-58. PMID: 1958709.Peer-Reviewed Original ResearchConceptsActive receptor tyrosine kinasesTissue-specific genesReceptor tyrosine kinasesSignal transmission pathwaysGrowth factor receptorLow molecular weight inhibitorsUnregulated expressionCertain chromosomesTyrosine kinaseGenesNormal melanocytesMalignant transformationMouse fibroblastsFactor receptorDrug designWeight inhibitorsKaryotypic changesKinaseMelanoma-prone familiesGrowth factorOncogeneHuman melanomaMelanocytesMelanoma growthTransmission pathways
1989
Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene
Kwon B, Haq A, Wakulchik M, Kestler D, Barton D, Francke U, Lamoreux M, Whitney J, Halaban R. Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene. Journal Of Investigative Dermatology 1989, 93: 589-594. PMID: 2507645, DOI: 10.1111/1523-1747.ep12319693.Peer-Reviewed Original ResearchConceptsMouse tyrosinaseTyrosinase geneMouse chromosome 7Mouse tyrosinase geneSomatic cell hybridsSouthern blot analysisChromosomal mappingGenomic clonesCell hybridsPromoter sequencesTATA elementAlbino locusChromosome 7Melanoma cell linesCDNA probeNormal melanocytesTyrosinase mRNABackcross miceBlot analysisFarthest upstreamCell linesDeletion miceGenesLociCloudman S
1988
Responses of Cultured Melanocytes to Defined Growth Factors
HALABAN R. Responses of Cultured Melanocytes to Defined Growth Factors. Pigment Cell & Melanoma Research 1988, 1: 18-26. DOI: 10.1111/j.1600-0749.1988.tb00790.x.Peer-Reviewed Original ResearchBasic fibroblast growth factorCyclic adenosine monophosphateGrowth factorSpecific growth factorsCell divisionHuman melanocyte culturesFibroblast growth factorNatural growth factorsNormal melanocytesCultured melanocytesStimulatory activityDifferentiated functionsMelanocyte proliferationMelanocyte culturesMelanocytesNormal fibroblastsAdenosine monophosphatebFGF as an autocrine growth factor for human melanomas.
Halaban R, Kwon BS, Ghosh S, Delli Bovi P, Baird A. bFGF as an autocrine growth factor for human melanomas. Oncogene Research 1988, 3: 177-86. PMID: 3226725.Peer-Reviewed Original ResearchConceptsBasic fibroblast growth factorNormal human melanocytesBFGF gene transcriptsHuman melanocytesGrowth factorAutocrine growth factorGene transcriptsHuman metastatic melanomaMolecular mechanismsFibroblast growth factorNormal melanocytesCyclic adenosine monophosphateSerum-containing mediumAnti-bFGF antibodyMelanoma cellsAbnormal expressionAdenosine monophosphateHuman melanomaMelanocytesRegular culture mediumDibutyryl cyclic adenosine monophosphateMitogenic activityCulture mediumCellsTranscripts