THE BIOLOGY OF CANCERA group of diseases identified by uncontrolled

cell growth and proliferation

Viruses Genetic make-up Immune status Radiation Carcinogens

Normal cell

growth

Abnormal cell

growth

DEVELOPMENT OF CANCERFirst Mutation Second Mutation

Third MutationFourth Mutation

Tumor formation Angiogenesis Invasion Metastasis

PROGRESSION OF CANCER

HyperplasiaDysplasia

In situ cancer

Invasive cancer

Mutation

THE CELL CYCLEProphase Metaphase Anaphase Telophase

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

CELL CYCLE CHECKPOINTS

G1 Checkpoint

Enter into S

Is environment favorable?

G2 Checkpoint

Is environment favorable?Has DNA replicated?

Enter into M Exit M

M Checkpoint

Are all chromosomes attached to the spindle?

CYCLIN-DEPENDENT KINASES (CDK) & CYCLINS

Mitotic cyclin(Cyclin B)

Mitotic cdk(cdk 1)

Active Mitosis Promoting Factor

Degradedmitotic cyclin

(Cyclin B)

S phase cdk(cdk2)

S phase cyclin(Cyclin A)

Active cdk2-cyclin A complex

DegradedS phase cyclin

(Cyclin A)

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

CYCLIN DEPENDENT KINASE INHIBITORS (CDKIs)

Inhibitors of Kinase 4(INK4s)

Cdk inhibitory proteins(CIPs)

RETINOBLASTOMA PROTEIN

Inactive Rb-E2F complex

Cyclin A – Cdk2 complex

Inactive Rb

Active E2F+

Enzyme forDNA synthesis

G1 phase S phase

Late G1 phase

Late M phase

CONTROL SWITCHES OF THE RESTRICTION POINT

Cyclin D–cdk4 Complex

Activation of cyclin 2 Inactivation of p16 Rb protein phosporylation