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Oncogenes et Gènes Suppresseurs de
Tumeurs Introduction
I. Les Conditions de la Prolifération
Cellulaire Les Conditions Normales Sénescence I
nhibition de Contact, Adhérence et Facteurs de
Croissance Transformation Cellulaire,
Définitions Le Développement Tumoral

II. Les Gènes Impliqués Dans les Contrôle
Cellulaire Anomalies Génétiques Oncogènes et
Gènes Suppresseurs de Tumeurs Hypothèse de
Knudson L Exemple de Rb
III. Découverte des Oncogènes Le Virus du
Sarcome de Roux Découverte de lAgent
Transformant src Les Protéines Cellulaires
Equivalentes Mode d Action des Oncogènes
L Exemple de T
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Gel retard
Les Activations Sont Transitoires
Western Blot
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Tumeurs
Mutations
Mutations
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Les Etapes du Développement Tumoral
 The Hallmarks of Cancer   Robert Weinberg
Cell, 2000, 100 57
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Genes involved in cancer
Oncogenes Activated from protooncogenes Usually
enhance cell proliferation Tumor suppressor
genes Inactivated by mutation or deletion Usually
arrest cell proliferation Genes regulating
apoptosis Control cell survival Overexpression,
mutation or deletion can enhance cell
survival Genes regulating metastasis Control
cell motility and interaction with the
environment Both activating and inactivating
mutations
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Detection of Oncogenes in Human Tumors
DNA transfections
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Activation of ras Oncogenes by Point Mutations
1 2 3 4 5 6 7 8
9 10 11 12 13

• Ras mutations in tumors usually involve codons
  12, 13, 59 and 61.
• Mutated ras is found in 50 of colorectal cancers
  and 95 of pancreatic cancers.

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Functions and Mechanisms of Activation of
Proto-oncogenes Products

• Protein phosphorylation.
• Can activate kinase activity of the protein.
• Can generate docking sites to recruit target
  proteins.
• Signal transmission by GTPases.
• Signal transduction.
• Ras family proteins are prototypical members.
• Proteins localized in nucleus.
• Control of progress through cell cycle.
• Involvement in DNA replication.
• Proteins that regulate cell death (apoptosis).

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From the Growth Factor to the Cell Cycle