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Lecture Outline: - Oncogenes - Tumor Suppressor Genes - Multiple Hit Hypothesis - Oncogene Addiction Hypothesis

This document provides an outline of a lecture on oncogenes and tumor suppressor genes. It discusses key topics including oncogenes, tumor suppressor genes, the multiple hit hypothesis, and the oncogene addiction hypothesis. Specific oncogenes mentioned include Ras, Raf, and MYC. Ras and Raf oncogenes result in constitutively active MAPK signaling and unregulated gene transcription. MYC oncogenes accumulate to high levels due to a point mutation and increase transcriptional activity, driving cells through the cell cycle. Common human oncogenes are also listed.

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0% found this document useful (0 votes)
45 views

Lecture Outline: - Oncogenes - Tumor Suppressor Genes - Multiple Hit Hypothesis - Oncogene Addiction Hypothesis

This document provides an outline of a lecture on oncogenes and tumor suppressor genes. It discusses key topics including oncogenes, tumor suppressor genes, the multiple hit hypothesis, and the oncogene addiction hypothesis. Specific oncogenes mentioned include Ras, Raf, and MYC. Ras and Raf oncogenes result in constitutively active MAPK signaling and unregulated gene transcription. MYC oncogenes accumulate to high levels due to a point mutation and increase transcriptional activity, driving cells through the cell cycle. Common human oncogenes are also listed.

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Vương Tú
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© © All Rights Reserved
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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

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