The Rb/CDK4/CyclinD Pathway is Dysregulated in
many human cancers
P16
Deletion/Mutation/
Methylation
Glioblastoma (70%)
Mesothelioma (55%)
Pancreatic (50%)
Rb
Inactivation:
Retinoblastoma (100%)
SCLC (90%)
NSCLC (30%)
Gliomas (14%)
Cdk4
Amplification/Mutation:
Amplified:
Sarcomas (18%)
Gliomas (18%)
Melanoma
•
E2F control genes essential for cell cycle progression
•
Retinoblastoma (Rb) susceptibility protein prevents progression from the G1 phase to S phase through its interaction with E2F
transcription family members
Dickson MA, Schwartz GK.
Curr Oncol
2009
Shapiro GI.
J Clin Oncol
2006
Pathway defects are usually exclusive and affect nearly 100% of cancers
Amplification
:
Head and Neck (43%)
Esophageal (34%)
Breast (13%)
Expression:
t(11;14) translocations
MC Lymphoma (most)
Myeloma (34%)
Cyclin D1-11q13
p16
G1
S phase
G2
M
Cyclin
D
Cdk4
E2F/DP1
Rb
/DP1
E2F/DP1
inactive
active
P
P
Rb
P
P
