THE BIOLOGY OF CANCER

1. THE BIOLOGY OF CANCER A group of diseases identified by uncontrolled cell growth and proliferation Normal cell growth Abnormal cell growth Viruses Genetic make-up Immune status Radiation Carcinogens

2. DEVELOPMENT OF CANCER First Mutation Second Mutation Fourth Mutation Third Mutation Tumor formation Angiogenesis Invasion Metastasis

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

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

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

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

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

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

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

10. CONTROL SWITCHES OF THE RESTRICTION POINT Cyclin D–cdk4 Complex Activation of cyclin 2 Inactivation of p16 Rb protein phosporylation