1. THE BIOLOGY OF CANCER A group of diseases identified by uncontrolled cell growth and proliferation VirusesGenetic make-upImmune statusRadiationCarcinogens Normal cell growth Abnormal cell growth

2. DEVELOPMENT OF CANCER First MutationSecond Mutation Third MutationFourth Mutation Tumor formationAngiogenesisInvasionMetastasis

3. PROGRESSION OF CANCER Hyperplasia Dysplasia In situ cancer Invasive cancer Mutation

4. THE CELL CYCLE ProphaseMetaphaseAnaphaseTelophase M G0 G2 Mitosis G1 S Cell increases in size & produces RNA and synthesizes proteins Cell arrest & absence of cell division DNA synthesis Production of new proteins for cell division G1 + S + G2 = Interphase

5. CELL CYCLE CHECKPOINTS G1 Checkpoint Enter into S Is environment favorable? G2 Checkpoint Is environment favorable? Has DNA replicated? Enter into MExit M M Checkpoint Are all chromosomes attached to the spindle?

6. CYCLIN-DEPENDENT KINASES (CDK) & CYCLINS Mitotic cyclin (Cyclin B) Mitotic cdk (cdk 1) Active Mitosis Promoting Factor Degraded mitotic cyclin (Cyclin B) S phase cdk (cdk2) S phase cyclin (Cyclin A) Active cdk2-cyclin A complex Degraded S phase cyclin (Cyclin A)

7. PHOSPHORYLATION OF CYCLIN-CDK COMPLEX CDK Cyclin Inactive cyclin-cdk complex Active cyclin-cdk complex (CAK) Cdk activating kinase Wee-1 Inactive cyclin B- cdk1 complex (Inactive MPF) Active cyclin B- cdk1 complex (Active MPF) cdc2 CAK

8. CYCLIN DEPENDENT KINASE INHIBITORS (CDKIs) Inhibitors of Kinase 4 (INK4s) Cdk inhibitory proteins (CIPs)

9. RETINOBLASTOMA PROTEIN Inactive Rb-E2F complex Cyclin A – Cdk2 complex Inactive Rb Active E2F + Enzyme for DNA synthesis G1 phaseS phase Late G1 phase Late M phase

10. CONTROL SWITCHES OF THE RESTRICTION POINT Cyclin D–cdk4 Complex Activation of cyclin 2Inactivation of p16Rb protein phosporylation