2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim H, Frederick DT, Levesque MP, Cooper ZA, Feng Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn MM, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai Z. Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation. Cell Reports 2015, 11: 1458-1473. PMID: 26027934, PMCID: PMC4681438, DOI: 10.1016/j.celrep.2015.04.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChromatography, LiquidDown-RegulationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHeterograftsHumansImmunoblottingImmunohistochemistryImmunoprecipitationJanus Kinase 1Mass SpectrometryMelanomaMiceMice, NudeProto-Oncogene Proteins B-rafRNA, Small InterferingTransfectionUbiquitin-Protein LigasesConceptsBRAF inhibitorsRTK expressionReceptor tyrosine kinasesRemarkable clinical responsesBRAFi-resistant melanomasInhibition of JAK1BRAFi-resistant tumorsClinical responseCombination therapyMost tumorsBRAF mutationsTumor specimensVivo xenograftsBRAFi resistanceMelanoma cellsElevated expressionMelanomaEGFRAdaptive resistanceTumorsRNF125MITF expressionTyrosine kinaseJAK1Downregulation
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
1996
Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia
Halaban R, Böhm M, Dotto P, Moellmann G, Cheng E, Zhang Y. Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia. Journal Of Investigative Dermatology 1996, 106: 1266-1272. PMID: 8752668, DOI: 10.1111/1523-1747.ep12348972.Peer-Reviewed Original ResearchConceptsTranscription factorsFibroblast growth factorBasic fibroblast growth factorMelanocyte-specific genesMelanogenic gene expressionTranscription factor microphthalmiaDownregulated transcription factorsDNA consensus siteTyrosinase-related protein 1Human metastatic melanoma cellsImmortalized mouse melanocytesPink-eyed dilutionCloudman S91 mouse melanomaMetastatic melanoma cellsSequestration of p300Transcriptional adaptorGrowth factorE1A mutantsConsensus sitesMouse melanocytesRegulatory proteinsMolecular basisOncogene RasGene expressionTumorigenic transformation
1991
Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes.
Ramon y Cajal S, Suster S, Halaban R, Filvaroff E, Dotto G. Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes. American Journal Of Pathology 1991, 138: 349-58. PMID: 1992762, PMCID: PMC1886204.Peer-Reviewed Original ResearchConceptsMalignant tumorsMorphologic featuresDifferent morphologic featuresMalignant melanomaBenign lesionsNude miceSyngenic miceSame tumorMelanocytic lesionsSmall round cellsBasic fibroblast growth factorH-RasFibroblast growth factorBenign melanocytic lesionsHistologic typeHistologic featuresSubcutaneous injectionBiologic behaviorSpindle cellsPossible molecular mechanismsEpithelioid cellsIntradermal nevusHuman melanomaLesionsDifferent tumors