Cancer pathology Flashcards
What is cancer?
a disease of aberrant cell proliferation & differentiation?
How high is the risk of cancer arising from functional ?
Low
What are 3 environmental influences must affect cancer?
- infection
- diet
- noxious agents
What is the Peyton Roux experiment?
“a sarcoma is transferred to a chicken”
What does cancer arise from?
Virus encodes a hyperactive form of a human tyrosine kinase gene
What are the effects of a hyperactive form of a human tyrosine kinase gene?
increased cell adhesion, cell proliferation, cell mobility
What is an example of a virus that causes cancer?
cervical carcinoma - caused by human papillomavirus
What is an example of a bacteria that causes cancer?
Gastric carcinoma - caused by helicobacter pylorii
What is an example of a cancer caused by diet?
Aspergillus oryzae - koji mold - rice, peanuts - can cause hepatocellular carcinoma
(caused by aflatoxin) - in order to get rid of this toxin, the liver causes a structural change, that modifies DNA bases, results in a mutation
What is an example of a noxious substance that causes cancer?
asbestos - causes mesothelioma
What other factor can cause cancer other than environmental factors?
Genetic predisposition
What is an example of a cancer caused by a genetic pre-disposition?
Breast cancer syndrome
What is an example of a cancer caused by genetic predisposition?
chronic myeloid leukemia
What is the chromosomal error that causes chronic myeloid leukemia?
there is a chromosomal translocation between chromosome 9 & chromosome 2
What technique is used to establish what chromosomal changes cause certain cancers?
FISH (fluorescent in situ hybridisation)
Why does chromosomal translocation have such a devastating effect on the proliferation of white blood cells?
Causes the fusion of 2 genes, one which is a positive regulator of cell growth
What is a kinase?
An enzyme that phosphorylates proteins. It changes the function of the protein. This can either turn a protein on or off.
What are oncogenes?
A gene with the potential to cause cancer, by transforming cellular behaviour
How do oncogenes come about?
Arises from genes involved in regulated proliferation - PROTO-oncogenes
What are the 2 structural shapes that Ras exists in?
Ras + GTP
Ras + GDP
When the ras is bound to GTP, is the protein switched on or off?
Switched on
When the ras is bound to GDP, is the protein switched on or off?
Switched off
How fast is the rate of conversion between ras + GTP/GDP without GTPase?
Rate of conversion is slow without GTPase.
What is the conversion from Ras + GTP to Ras + GDP called?
exchange
What do growth factors bind to, in order to start cells proliferate?
receptors - e.g. tyrosine kinase receptors
What are the different pathways which encourage cell growth from ras?
- cell growth
- gene expression
- gene morphology & movement
Describe the state of mutant ras in tumors?
In mutant ras, the off ras state doesn’t exist. This is because ras loses its GDP.
What is the argument for the existence of tumour suppressor genes?
loss of growth suppressor gene more likely than gain-of-function oncogenes mutations.
What is the argument against the existence of tumour suppressor genes?
loss of both alleles of putative growth suppressor genes unlikely
What theory did Knudsen propose?
one/two-hit hypothesis
Why is Knudsen’s one/two-hit hypothesis important?
provides evidence:
- for tumour suppressor gene hypothesis
- that cancer requires wild-type alleles
- for the basis of inherited predisposition to cancer
A Chromosome 13 deletion can create what cancer?
retinoblastoma
Describe the properties of oncogenes
- activating
- gain of function
- dominant
- one allele mutated required to exert effect
- enhanced effect on the function of the protein product
Describe the properties of tumour suppressor genes
- inactivating
- loss of function
- recessive
- two allele mutated required to exert effect
- reduced effect on the function of the protein product
How genetically stable are cancer cells?
cancer cells are genetically unstable
What are the 3 causes of genetic instability?
Defects in:
- DNA repair pathways
- Correction mechanisms for DNA replication errors
- Correction mechanisms for DNA segregation errors
What is an example of a cellular stress that can induce apoptosis in normal cells?
DNA damage
