Flashcards in Oncogenes and Tumour Suppressor Genes Deck (19)
What are the six hallmarks of cancer?
Disregard of signals to stop proliferating
Disregard of signals to differentiate
Capacity for sustained proliferation
Evasion of apoptosis
Ability to invade
Ability to promote angiogenesis
What is gene amplification?
Production of multiple gene copies
What are chimeric genes?
Genes that are formed by combinations of portions of one or more coding sequence to produce new genes (e.g. the swapping of tips of chromosomes)
When can the formation of chimeric genes be a problem?
If one of the pieces of translocated DNA is a promoter, it could lead to upregulation of the other gene portion (this occurs in Burkitt’s lymphoma)
If the fusion gene codes for an abnormal protein that promotes cancer
What is the Philadelphia Chromosome?
Chromosome produced by the translocation of the ABL gene on chromosome 9 to the BCR gene on chromosome 22
The BCR-ABL fusion gene encodes a protein that promotes the development of cancer
State some important oncogenes in human cancers.
SRC – tyrosine kinase
Myc – transcription factor
JUN – transcription factor
Ha-Ras – membrane bound GTPase
Ki-Ras – membrane bound GTPase
What is an example of an inherited cancer?
Retinoblastoma – malignant cancer of the developing retinal cells
What mutation causes retinoblastoma?
What are the functional classes of tumour suppressor genes?
Regulate cell proliferation
Maintain cellular integrity
Regulate cell growth
Regulate the cell cycle
Nuclear transcription factors
DNA repair proteins
Cell adhesion molecules
Cell death regulators
State some important tumour suppressor genes in human cancers
P53 – cell cycle regulator
BRCA1 – cell cycle regulator
PTEN – tyrosine and lipid phosphatase
APC – cell signalling
In what form is p53 inactive?
When it is bound to MDM2
What is p53 important for?
It is important for regulation of p53 target genes (involved in DNA repair, growth arrest, senescence etc.) and protein-protein interactions (e.g. apoptosis)
What is odd about p53 considering it is a tumour suppressor gene?
It acts in a DOMINANT manner –mutation of a single copy is sufficient to achieve dysregulation of activity
What deletion causes loss of the APC gene?
What is APC involved in?
What is the risk of people with this mutation developing colon cancer?
What signalling pathway is APC involved in?
What is the main role of APC that prevents uncontrolled growth?
It breaks down beta-catenin so that it doesn’t bind to LEF1 and promote uncontrolled proliferation