Table of Contents
Biol 568 Advanced Topics in Molecular Genetics
Oncogenes and Cancer
Cancer Cell Phenotypes
Terminology
Terminology
Primary cell culture
Fig 30.4 Cancer Cell Properties
Cell Properties
Cell Properties
Cell Properties
in vitro vs. in vivo
Cell Properties
Fig 30.6 EM of normal and transformed cells
Genetic Basis
Genetic Basis
Oncogenes
Oncogenes
Tumor suppressor genes
Transformation of Cells
Fig 30.4 Transforming viruses may carry oncogenes
Fig 30.9 Permissive vs. nonpermissive cells
Permissive vs. Non-Permissive
Fig 30.10 Transformation by viruses: adenovirus or polyomavirus
Fig 30.11 Genetic transfer by retroviruses: horizontal or vertical transfer of genetic info
Transforming Retroviruses
Transforming Retroviruses
Fig 30.12 Acute transforming retrovirus
Fig 30.14 Oncogenes of transforming retroviruses
Difference in v-onc and c-onc
Expression of the v-onc sequence is capable of transformation
2 Models for Oncogenicity
Difference in v-onc and c-onc
Difference in v-onc and c-onc
v-onc vs. c-onc genes
Level of Expression also Important
Fig 30.15 Transfection assay
Transforming Activity
Isolated Transforming Genes
ras transforming gene
ras oncogenes
ras proto-oncogene
signal transduction pathway
signal transduction pathway
Fig 30.16 Ras Activity
Fig 30.16 Ras Activity
Fig 30.16 Ras Activity
Activation of protooncogenes
Oncogene Amplification
Activation by Retroviral Insertion
Fig 30.17 Insertion of ALV at c-myc locus
Fig 30.17 Insertion of ALV at c-myc locus
Fig 30.17 Insertion of ALV at c-myc locus
Coding sequence of c-myc does not change
PPT Slide
Fig 30.18 Reciprocal chromosomal translocation
c-myc activation by translocation
c-myc and tumorigenic phenotypes
c-myc and tumorigenic phenotypes
c-myc and tumorigenic phenotypes
c-myc activation
Philadelphia Translocation
Figure 30.19
Why is Bcr-Abl fusion oncogenic?
Oncogenes
Signal Transduction Cascade
Fig 30.20 Different Types of Oncogenes
Fig 30.20 Different Types of Oncogenes
Fig 30.20 Different Types of Oncogenes
Common feature
Oncogenes
PPT Slide
Transmembrane receptors
Ligand binding induces receptor dimerization
Fig 30.21 Activation of GF receptor
v-erb
v-erb
Oncogenes
src as prototype cytoplasmic tyrosine kinase
Fig 30.22 Src protein domains
Comparison of c-src and v-src
Src Phosphorylation see Fig 30.23
Control of src activity by phosphorylation
Control of src Activity by Phosphorylation
Fig 30.24 Receptor tyrosine kinase (src) activation
Control of src Activation
Oncogenes
PPT Slide
v-Oncogenes
v-Rel
Fig 30.26: Function of oncogenic factors
AP1
Fig 30.26 Function of oncogenic factors
v-erbA
v-erbA
Fig 30.26: Function of oncogenic factors
c-jun, c-rel, c-fos, c-myc
Transformation by Adenovirus E1A oncogene
Fig 30.27 Adenovirus E1A region is spliced to form three transcripts
Adenovirus E1A Oncogene
Tumor Suppressor Genes
Retinoblastoma (Rb)
Fig 30.28 Retinoblastoma
Rb protein
Target proteins of Rb
Fig 30.29 Rb and the cell cycle
Tumor Suppressor Rb
Fig 30.30 Tumor suppressors and cell cycle control
Other cell cycle control proteins
Tumor Suppressor p53
Fig 30.32 p53 Activity
p53
p53 - tumor suppressor
p53 mutations
Tumor suppressor p53
Fig 30.33 DNA damage activates p53
Activated p53 Function
Fig 30.34 p53 functional domains
p53 functional domains
p53 functional domains
p53 regulator of transcription
p53 Function
Model for p53 Activation
p53 mutations
Fig 30.35 Pathways activated by p53
Fig 30.35 Pathways activated by p53
Fig 30.35 Pathways activated by p53
p53 Regulation
Fig 30.36 Inactivation of p53
Fig 30.37 p53 interactions
Control of p53
p53 (and Rb) are regulated by multiple pathways
p53 (and Rb) are regulated by multiple pathways
Control of p53
Fig 30.38 p53 modifications
Targets for various pathways located in the terminal regions
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