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CellCycleRegulation-PartII
Dhyan Chandra, Ph.D.Department of Pharmacology and TherapeuticsL4-305, Center for Genetics and Pharmacology
Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo
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Topics to be discussed • Recap of the last cell cycle lecture • Alteration of cellular signaling in cancer • Cell cycle and apoptosis • Differences between cancer and normal cells • Cell cycle regulation in lung carcinogenesis • The role of ROS in cell cycle
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Cyclinexpressionduringcellcycle
cyclinB
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Controlofcyclinlevelsduringthecellcycle
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(A-CDK1) (B-CDK1)
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Controlofcyclinadvancebyextracellularsignals
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Positive-feedbackloopsandirreversibilityofcellcycleadvance
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Positive-feedbackloopsandirreversibilityofcellcycleadvance
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Alterationofcellularsignalingincancer
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ControlofcyclinDlevels
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ControlofcyclinD1levelsbyRas
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ActionofMyconcellcycle
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ActionofMyc-ER(estrogenreceptor)oncellcycle
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MycinhibitscelldifferentiationbyID(inhibitorofdifferentiation)
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PerturbationoftheR-pointtransitioninhumantumorsRed:favorscellcycle Blue:inhibitscellcycle Gray:notknowntochangecellcycle
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Regulationandactivitiesofp53andE2F
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IaquintaandLeesCurrentOpinioninCellBiology2007
E2Ftargetsareshowninred
p53targetsareshowninblue
TargetsforE2Fandp53-purple
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E2F1regulatesp53andthusapoptosis
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Differencesbetweencancerandnormalcells
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Contrasting schemes of the proposed response of normal and cancer cells to mitogens.
Zwang Y et al. Cancer Res 2012;72:1051-1054
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Cellcycleregulationinlungcarcinogenesis
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EyminandGazzeriCellCycle2009
Darkgrey:overexpressedLightgrey:lossofexpression
Abnormalitiesofcellcycleregulatorsinhumanlungtumors
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EyminandGazzeriCellCycle2009
Alterationsincomponentsofcellcyclecheckpointsinlungtumors
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EyminandGazzeriCellCycle2009
AlterationsoftheG1/StransitionregulatorsinNSCLCvsSCLC
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TheroleofROSincellcycle
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Mitochondria
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Mitochondrial respiratory chain
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KobayashiandSuda,jCellPhysiol2011
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WangandYi,CancerBiologyandTherapy2008