Cancer extra notes Flashcards
what do proto-oncogenes code for?
essential proteins involved in maintenance of cell/ division/ differentiation
How can proto-oncogenes become carcinogenic?
- mutation
- gene amplification
- chromosomal translocation
- insertional mutagenesis
what is the SRC gene and what cancers is it involved in?
- tyrosine kinase
- overexpression = breast/colon/lung
what is the MYC gene?
- TF
- translocation = Burkitt’s lymphoma
what is the JUN gene?
- TF
- overexpression/deletion = lung
what is the Ha-RAS gene?
- G protein
- point mutation = bladder
What is the Ki-RAS gene?
- G protein
- point mutation = colon, lung
what is p53 and what cancers is it involved in?
- cell cycle regulator
- colon, breast, bladder
what is BRCA1 and what cancers it it involved in?
- cell cycle regulator
- breast, ovarian, prostate
what is PTEN?
- tyrosine and lipid phosphatase
- prostrate, glioblastoma
what is APC?
- cell signalling
- colon
what happens in the caspase cascade?
- once apoptosis is initiated, initiator caspases cleave and activate effector caspases
where are death receptors found? when are they activated?
- found on all cells on surface
- only activated when they encounter death ligands
describe the death receptor signalling process
- death ligand binds to death receptor
- death receptor undergoes trimerisation (brings 3 cytoplasmic DD domains together)
- trimersised death domains recruit positive adaptive protein FADD
- this binding causes recruitment and oligomerisation of procaspase 8
- binding of caspase 8 to FADD –> formation of DISC
- DISC formation results in cross activation of procaspase 8
- caspase 8 released, cleaves effector caspases
what are the 2 categories in the Bcl-2 family?
- anti-apoptotic proteins (Bcl-2, Bcl-XL): mitochondrial membrane
- pro-apoptotic proteins (Bid, Bad, Bax): cytosol or mitochondrial membrane
explain how growth factors go about having an anti-apoptotic effect
- GF binding = dimerization = phosphorylation of tyrosine kinase receptors
- initiates signal transduction pathways and creates docking sites for adaptor proteins
- Grb2 binds and mediates Ras pathways = cell growth
- another phosphorylation site triggers PI3-kinase pathway
what is PI3-K? describe its structure?
lipid kinase
involved in growth control and cell survival
- has targeting, adaptor and catalytic subunits
describe the MoA of PI3-K?
- phosphorylates PIP2 to PIP3
- recognised by adaptor subunit of PKB
- PKB recruited to cell membrane
- is activated w/ anti-apoptotic effects
- PKB phosphorylates Bad
what happens when GFs are absent?
- PkB fails to come to cell membrane
- Bad phosphorylated and released from its heterodimer
- Bad goes to mitochondrial membrane
- Binds to BH3 domain on anti-apoptotic Bcl-2, displace pro-apoptotic Bcl-2
- once pro-apoptotic are released, form a pore
- this allows cytochrome C to escape into cytosol and induces apoptosis
what are the roles of PKB?
- phosphorylates and inactivates Bad
- phosphorylated and inactivates capsape 9
- inactivated FOXO transcription genes
- stimulation of protein synthesis (MAPK/ERK)
state the 2 extrinsic regulators of apoptosis
- PTEN
- IAPs
what is PTEN?
- lipid phosphatase
- counteracts production of PKB
- reduces regulation of cell survival and promotes apoptosis
what is IAPs?
- regulate programmed cell death by binding to procaspases
- prevent their activation
- binds to active caspases and inhibits their activity
what do replicated chromosomes consist of?
- 2 pairs of sister chromatids
- each w/ kinetochore and central centromere
what is a centrosome made up of?
- 2 centrioles (made up of microtubules)
what is ampehlic attachment of spindle to kinetochores?
- normal
- kinetochores do not produce checkpoint signal
what is merotelic attachment?
- spindle attachment from same centrosome to both kinetochores
- bad because kinetochores still don’t produce checkpoint signal
- don’t know its abnormal
what is monotelic attachment?
- movement of both pairs of chromatids to same pole through attachment of 1 centrosome to 1 kinetochore
- no attachment to other
- will produce checkpoint signal
what is syntelic attachment?
- movement of both pairs of chromatids to same pole
- attached to different spindles
- both sister chromatid pairs are at same pole
- one daughter cell has no chromosomes after cytokinesis
what is the activity of Cdks regulated by?
their interaction with cyclins and their phosphorylation
which cdk/cyclin is found in M phase?
cdk1-cyclin B
which cdk/cyclin is found in S phase?
cdk2-cyclin A
which cdk-cyclin is found in G1 phase?
cdk2-cyclin E
which cdk-cyclin is found in transition from G0 to G1?
cdk4/6-cyclin D
describe the model of sprouting angiogenesis
- need for new blood vessels
- GFs released that activate endothelial cells in pre-existing capillaries
- endothelial cells undergo conformational change
- go from being organised monolayer to sending out filopodia
- migrate towards GFs
- cytoskeleton of tip cell must be modified
- tip cells keep on moving until they find another tip cell
- they fuse and stabilise
what does angiopoietin 1 do?
when it binds to Tie2, promotes quiescence in vasculature
what does angiopoietin 2 do?
gets released when you need to form new blood vessels or need to respond to inflammation
what are the 5 types of malignant melanoma?
- superficial spreading
- nodular
- lentigo maligna melanoma
- acral lentiginous
- amelanotic
what does listeria express at one pole of the bacterium? what does it mean?
- ActA
- can bind actin in host cytoplasm
- only sufficient to allow limited motility
how does listeria get full motility?
- needs VASP binding to proline-rich region of protein
- VASP recruits Arp complexes (inc. rate of comet tail formation)
- also binds proffilin to this part of cell (ensures good supply of ATP-containing G-actin)
what happens when the bacterium is in the acidic environment of phagolysosome?
- produces lysin protein
- protein breaks down organelle membrane
- listeria enters cytoplasm
