@derka 1. An explanation should be as simple as possible but not a bit simpler… Albert Einstein 2.
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Transcript of @derka 1. An explanation should be as simple as possible but not a bit simpler… Albert Einstein 2.
5
G0
G1 checking point
S phase
G2-checking point
To be or not to be…an intracellular drama A computo-novella
Mitosis
Functional significance of genes in melanoma
DNA break
hMutShMSH2hMSH6}
hMIH1hPMS2
hMutL}
MMR (Mismatch Repair Mechanisms)
ATM
BRCA1
P
P
BRCA2 RAD51
BRCA1 RAD52 Repair
Gene for repair ofdouble strand breaks
Apoptosis
p53
+
p21
DeVita p.20056th Edition
Cyclin dependentKinase (cdk2)
Cyclin E}
RB E2F
RBP
E2F
Cell cycleactivation
Cycle arrest2
+
p16Cyclin dependentKinase (cdk4/6)
Cyclin D
}
MLH1PMS1PMS2
p27
TGF- NEJM 342:1350,2000
INK4 familyINK4 family
p15
p18
p19
cip/kip family
p57
Growthfactors
Growth receptors mediated growth stimulation
EGF receptor
EGF
TK TK
Grb2adapter
p21 rasinactive
MAP kinases
jun
+ P
fos
+ P
jun fos
P P
myc Cyclin D
TK=Thyrosine kinase
3
p21 rasactive
AKT
Proliferationsignals
Glucosemetabolism
Energy
Protein synthesis
Anti-apoptosis
Enhanced angiogenesis
PTEN
-
MAP = Mitogen activated protein kinase
P
SH2
GEF
GEF = Guanine exchange factor
GDP GTP
GAP
GAP= GTPase activating protein
Apoptosis mechanismsApoptosis mechanisms
Mitochondria
BCL-2
Bax Bid
Cytochrome C AIF
Cytochrome C AIF
Caspases
Apoptosis
18
BadBik
P53
+
CathepsinD
TNF
FAS
Ceramide
Apoptosis
EGF receptor
EGF
TK
TK=Thyrosine kinase
6
Enhanced angiogenesis
Proliferationsignals
MAP kinases
MAP = Mitogen activated protein kinase
Grb2adapter
P
GEF
GEF = Guanine exchange factor
p21 rasinactive
GDP
p21 rasactive
GTP
GAP
GAP= GTPase activating protein
Anti-apoptosis
Glucosemetabolism Energy
Protein synthesis
Ribosomebiosynthesis
jun
+ P
fos
+ P
jun fos
P P
myc
Erbitux
IressaHerceptin
Antiangiogenic factors
Cyclin D
Cell proliferation
Akt/PKB
Akt/PKB=Protein kinase B
9
Functional significance of genes in melanoma
DNA break
hMutShMSH2hMSH6}
hMIH1hPMS2
hMutL}
MMR (Mismatch Repair Mechanisms)
ATM
BRCA1
P
P
BRCA2 RAD51
BRCA1 RAD52 Repair
Gene for repair ofdouble strand breaks
Apoptosis
p53
+
p21
DeVita p.20056th Edition
Cyclin dependentKinase (cdk2)
Cyclin E}
RB E2F
RBP
E2F
Cell cycleactivation
Cycle arrest2
+
p16Cyclin dependentKinase (cdk4/6)
Cyclin D
}
MLH1PMS1PMS2
p27
TGF- NEJM 342:1350,2000
INK4 familyINK4 family
p15
p18
p19
cip/kip family
p57
G0
G1 checking point
S phase
G2-checking point
To be or not to be…an intracellular drama
Growthfactors
A computo-novella
Mitosis
Growth receptors mediated growth stimulation
EGF receptor
EGF
TK TK
Grb2adapter
p21 rasinactive
MAP kinases
jun
+ P
fos
+ P
jun fos
P P
myc Cyclin D
TK=Thyrosine kinase
3
p21 rasactive
AKT
Proliferationsignals
Glucosemetabolism
Energy
Protein synthesis
Anti-apoptosis
Enhanced angiogenesis
PTEN
-
MAP = Mitogen activated protein kinase
P
SH2
GEF
GEF = Guanine exchange factor
GDP GTP
GAP
GAP= GTPase activating protein
Apoptosis mechanismsApoptosis mechanisms
Mitochondria
BCL-2
Bax Bid
Cytochrome C AIF
Cytochrome C AIF
Caspases
Apoptosis
18
BadBik
P53
+
CathepsinD
TNF
FAS
Ceramide
Apoptosis
G1-checking point
p21
DeVita p.20056th Edition
Cyclin dependentKinase (cdk2)
Cyclin E}
RB E2F
RBP
E2F
Cell cycleactivation
Cycle arrest10
p16Cyclin dependentKinase (cdk4/6)
Cyclin D
}
G1-checking point
DNA break
MMR (Mismatch Repair Mechanisms)
ATM
P
BRCA2 RAD51
BRCA1 RAD52
Gene for repair ofdouble strand breaks
DeVita p.20056th Edition
p53
Apoptosis
Cyclin dependentKinase (cdk2)
Cyclin E
Cycle arrest
p21
hMutShMSH2hMSH6}
hMIH1hPMS2
hMutL
MLH1PMS1PMS2
Cyclin Dp16
cdk4
RbE2F
E2F
BRCA1 P
P
Growth stimulation
Repair
Stop
G1-checking point
DNA break
MMR (Mismatch Repair Mechanisms)
ATM
P
BRCA2 RAD51
BRCA1 RAD52
Gene for repair ofdouble strand breaks
DeVita p.20056th Edition
Cyclin dependentKinase (cdk2)
Cyclin E
Cycle arrest
p21
E2F
P
Growth stimulation
Repair
Stop
Apoptosis
hMutShMSH2hMSH6}
hMIH1hPMS2
hMutL
MLH1PMS1PMS2
BRCA1 P
p53
E2FRbCyclin D
p16cdk4
EndometriumOvaryBreastStomachSmall bowelPancreasHepato-biliaryRenal pelvisUreter
HNPCC
Turcot
LynchSyndr.
ColonEndometriumRenal pelvisUreterSmall bowelBreast
G1-checking point
DNA break
MMR (Mismatch Repair Mechanisms)
ATM
P
BRCA2 RAD51
BRCA1 RAD52
Gene for repair ofdouble strand breaks
DeVita p.20056th Edition
Cyclin dependentKinase (cdk2)
Cyclin E
Cycle arrest
p21
E2F
P
Growth stimulation
Repair
Stop
Apoptosis
hMutShMSH2hMSH6}
hMIH1hPMS2
hMutL
MLH1PMS1PMS2
BRCA1 P
p53
E2FRbCyclin D
p16cdk4
E6
E7
Papilloma virus
AgentsAgents
• Hepatitis B
• Hepatitis C
• HIV-1
• HTLV-1
• HPV
• Epstein-Barr
Site of CancerSite of Cancer
Liver
Liver
Kaposi’s sarcoma
Adult T-cell lymphoma
Uterine cervix
Burkitt’s lymphoma, nasopharynx,Hodgkin’s disease
Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.22
Virus-related cancers