Cancer Genes Flashcards
(12 cards)
Function of Oncogenes
Most encode proteins involved in signaling:
- Growth factors Ligands
- Growth factor receptors
- Intracellular signal transmission
- Nuclear transcription factors
Essentially
Increased cell proliferation AND
Impair normal cell differentiation
Activation of Oncogenes
Gene amplification
Over expression of gene (mutation in gene promoter region)
Critical mutations
* Eg missense mutations
Chromosome Translocations
Example of Gene amplification causing cancer
Her2 in breast cancer
Activation of Oncogenes
- 3 main outcomes from mutation causing proto to oncogene and their effects
Mutation within the gene
- Hyperactive protein in normal amount
Mutlple copies of the gene
- Normal protein in excess
Gene moved to new DNA locus, under new control
- Normal protein in excess
Lecture Slide
How do chromosome translocations
activate proto-oncogenes?
Example
Form fusion gene which encodes for novel
protein with increased activity
Increased expression of oncogene
Myc translocations in Burkitts
Lymphoma
Tumour Suppressor Genes
- role
- how does it happen
-Example of two hit hypothesis
Recessive acting or “anti-oncogenes”
-requires loss of activity – of both alleles
Often mechanism in familial cancers – one
inherited mutation in TS gene with second
acquired mutation causing loss of activity of
the other allele
Retinoblastoma
Visual diagram of apoptosis normal vs abnormal
LEcture Slide
Generally in cancer what Genes are affected to prevent apoptosis
Upregulation of genes which encode for proteins that block apoptosis
Loss of activity of genes which encode for proteins that mediate apoptosis eg fas, p53
General Cancer process flwochart
Mutation inactivates tumor suppressor gene
Cells proliferate
Mutation inactivates DNA repair gene
Mutation of proto oncogeen cerates oncogene
Mutation inactivates severeal more TSG
Cancer
Lecture Slide
CML clinical features
*High white blood cell count
*Splenomegaly
*Chromosomal abnormality (9;22 translocation)
Describe the translocation that causes chronic myeloid leukemia
The ABL region of chromosome 9 swaps with the terminal end (BCR region) of 22. They swap leading to BCR-ABL leading to fusion protein with tyrosine kinase activity.
This forms the target for therapy and to see the response to therapy
How is Bcr-Abl used as a Therapeutic Target
and what medication is used
Lecture Slide
ATP in BCR-APL protein is targeted. As if the ATP can not be made then tyrosine cant be activated leading to lack of subsrate and effector binding together
Imatinib
