Lecture Outline

Oncogenes
Tumor Suppressor Genes
Multiple Hit Hypothesis
Oncogene Addiction Hypothesis

Oncogenes
Oncogene: onco (cancer) gene
1989 Nobel Prize in Medicine or
Physiology: The Discovery of the Cellular
Origin of Retroviral Oncogenes
J. Michael Bishop (UCSF)
Harold Varmus (UCSF)

Oncogenes Contd
Proto-oncogenes: normal cellular genes
usually involved in cell growth and/or cell
division
Oncogenes: a proto-oncogene that has
been activated by mutation or
overexpression. Results in a dominant
gain of function phenotype
Growth Factors, Growth Factor Receptors,
G-proteins, Kinases, Gene Regulatory Proteins

Oncogene Activation

Molecular Biology of the Cell. Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York and London: Garland Science;
c2002

Ras/Raf Oncogenic Signaling

The Cell - A Molecular Approach. Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Ras and Raf oncogenes are constitutively active

persistant
MAPK signaling
unregulated gene transcription

MYC Oncogene
Normal nondividing cells
Myc levels are low but responsive to growth
signals from the cellular environment

Dividing cells
Myc levels constantly maintained at an
intermediate level throughout cell cycle

Oncogenic MYC
Point mutation prevents MYC degradation
allows for accumulation of high levels of MYC
Increased transcriptional activity

MYC and the Cell Cycle

MYC

Degradation of p27
(CDK inhibitory protein)

Increased activity of Cyclin/CDK complexes

Phosphorylation of inhibitory Rb protein

Increased activity of E2F

G1

Cells continue through cell cycle

Common Human Oncogenes

The Cell - A Molecular Approach. Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000