Cell Cycle Regulation-Part II - Roswell Park …...Cell Cycle Regulation-Part II Dhyan Chandra,...
Transcript of Cell Cycle Regulation-Part II - Roswell Park …...Cell Cycle Regulation-Part II Dhyan Chandra,...
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
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
Cyclinexpressionduringcellcycle
cyclinB
Controlofcyclinlevelsduringthecellcycle
(A-CDK1) (B-CDK1)
Controlofcyclinadvancebyextracellularsignals
Positive-feedbackloopsandirreversibilityofcellcycleadvance
Positive-feedbackloopsandirreversibilityofcellcycleadvance
Alterationofcellularsignalingincancer
ControlofcyclinDlevels
ControlofcyclinD1levelsbyRas
ActionofMyconcellcycle
ActionofMyc-ER(estrogenreceptor)oncellcycle
MycinhibitscelldifferentiationbyID(inhibitorofdifferentiation)
PerturbationoftheR-pointtransitioninhumantumorsRed:favorscellcycle Blue:inhibitscellcycle Gray:notknowntochangecellcycle
Regulationandactivitiesofp53andE2F
IaquintaandLeesCurrentOpinioninCellBiology2007
E2Ftargetsareshowninred
p53targetsareshowninblue
TargetsforE2Fandp53-purple
E2F1regulatesp53andthusapoptosis
Differencesbetweencancerandnormalcells
Contrasting schemes of the proposed response of normal and cancer cells to mitogens.
Zwang Y et al. Cancer Res 2012;72:1051-1054
Cellcycleregulationinlungcarcinogenesis
EyminandGazzeriCellCycle2009
Darkgrey:overexpressedLightgrey:lossofexpression
Abnormalitiesofcellcycleregulatorsinhumanlungtumors
EyminandGazzeriCellCycle2009
Alterationsincomponentsofcellcyclecheckpointsinlungtumors
EyminandGazzeriCellCycle2009
AlterationsoftheG1/StransitionregulatorsinNSCLCvsSCLC
TheroleofROSincellcycle
Mitochondria
Mitochondrial respiratory chain
KobayashiandSuda,jCellPhysiol2011
WangandYi,CancerBiologyandTherapy2008