oncogenes and TSG Flashcards
in general terms, what gives rise to cancerous cell behaviour?
mutations and epigenetic changes
what is metastasis?
cancer cells invade surrounding tissues and remote organs
what does evolution of a tumour depend on?
microenvironment provided by stromal cells
what are the 2 cancer critical genes?
proto-oncogenes
tumour suppressor genes
how do proto-oncogenes drive a cell towards cancer?
gain of function mutation
how do TSG contribute towards cancer?
loss of function mutation
what are pathways that are damaged in tumours?
p53 pathway
Rb pathway
RTK/Ras/PI3K
what is p53 pathway responsible for?
regulates responses to stress and DNA damage
what is the Rb pathway responsible for?
initiation of the cell division cycle
what is the RTK/Ras/PI3K pathway responsible for?
signals for cell growth and division from outside cell in to the cell
what is p53 protein function?
transcription factor
what does p53 activation lead to?
cell cycle arrest (G1/G2)
senescence or apoptosis which prevent propagation of damaged DNA
what causes Li-Fraumeni syndrome?
loss of function mutation in TP53
what stage in the cell cycle do cells grow in prep for DNA replication?
G1
how may the 1st copy of TSG be inactivated?
chromosomal deletion/ inactivated by point mutation
how may the 2nd copy of TSG be lost?
errors in chromosome segregation, mitotic recombination, or gene conversion.
what are epigenetic changes that can permanently inactivate a TSG?
methylation
DNA packaging
how is p53 lost by targeted degradation?
HPV activates E3 enzyme
E3 enzyme ubiquitinates p53
what is ubiquitin?
a protein TAG attached to a protein that targets it for degradation
how is p53 lost by gene mutation?
monoallelic mutation may confer a dominant-negative function on TSG products
what is retinoblastoma?
rare childhood tumour in the neural precursor cells of the retina
how does retinoblastoma occur?
Deletions in chromosome 13
Rb gene which encodes Rb protein – a key suppressor of the cell cycle progression.
what are oncogenes?
tumour promotors
what are types of over activity?
deletion/ point mutation in coding sequence
mutation in regulatory region of gene
gene amplification
chromosome rearrangement
