4 Viruses and Cancer Flashcards
what does HBV and HCV cause
hepatocellular carcinoma
what does EBV cause
nasopharyngeal carcinoma
Burkitt’s lymphoma
Hodgkins disease
what does HPV cause
cervical carcinoma
what does HHV-8 cause
Kaposi’s sarcoma
what does HTLV-1 cause
adult T cell leukaemia/lymphoma
what does MCV cause
Merkel cell cancers
Criteria viruses and cancer
- epidemiology
- virus in tumour tissue
- mechanisms of oncogenesis
Mechanisms of Oncogenesis
- modulation of cell cycle control
- modulation of apoptosis
- ROS mediated damage
- additional events
cell cycle S
synthesis
cell cycle G2
Gap 2
cell cycle M
mitosis
cell cycle G1
Gap 1
cell cycle G0
resting
what happens in S phase
viral transcription
what is formed after S phase
DNA replication proteins (viral DNA replication)
Cyclin D pathway - G0
no cell cycle as E2F bound by protein complex (mainly made of Rb)
viral cell cycle
E2F switches cell on - cell cycle genes and leads to proliferation
Cyclin D – cyclin dependent kinases, needs phosphorylation of Rb, releases E2F represses
Cyclin E activated
E2F can drive cellular expression
Modulation of Apoptosis
Normal cells
Cell proliferating – cell is transformed
Permitted by transformation become benign tumour
Local invasion and proliferation
Early metastasis (spreading)
Metastatic cancer and resistance to therapy
what leads to appoptosis e.g.
loss of pro-apoptotic signals
checkpoint defect
oncogene activation
mutation of DNA damage sensing system
what are used to modulate apoptosis
- p53
- Bcl-2
- FLICE inhibitory proteins
what is P53
transcription factor - tumor suppressor activity
what happens to P53 if have cancer
No human cancer that cell expresses functional P53
what activates BH3
stress signal
what happens when BH3 is activated
leads to apoptosis
ROS Damage effect of inflammatory response
generate radicals, including OH. and NO.
free radicals
what does ROS damage
> DNA (mutation)
protein (nitration, nitrosation)
RNA
lipids (lipid peroxidation)
how do free radicals promote cancer e.g.
- mutating cancer related genes
- activating signal transduction pathways
what happens to any cell not expressing P53
die
what percentage of cancers are caused by viruses
15-20%
what do viruses that cause cancer have in common
all cause chronic infections
why do viruses cause cancer
don’t on purpose
for them to function - critical viral lifecycle
cause cancer due to the things they need to do to maintain their lifecycle
is a chance outcome
epidemiology example
hep B causes hepatocellular carcinoma
high links seen in sub-Saharan Africa
what is hepatocellular carcinoma
primary liver disease
why might there be no link of hep B and hepatocellular carcinoma in e.g. spain
high cancer
low hep B
- other factors cause cancer e.g. drinking alcohol
- may intervene with vaccines
what must stop for cancer to occur
stop apoptosis
what is Bcl-2 function
in mitochondria membrane controls the permeability, when proteins from mitochondria leak into cytoplasm = apoptosis
what is p53 function
increases mitochondrial membrane permeability
what is FLIPS function
FLICE inhibitory proteins
surface receptors that transmit apoptotic signals
examples of radicals
OH.
NO.
how does merkel cell virus cause cancer
infection in childhood
stay low level as
BUT immunosuppression occurs e.g. age, immunocompromised (AIDS), transplant = increase frequency of replication
virus integrate into DNA - insert randomly into genome
second mutation = helicase inactivation
lead to merkel cell carcinoma
how can viruses overcome cells to drive cell cycle
- prevent Rb suppressing cell cycle
> phosphorylate
> complex with activating proteins (change Rb from suppressing to activating)
> lift off promoter
what is Rb
retinoblastoma - tumour supressor gene
