CANCER Flashcards
2 ways in which cell division can become out of control
1) uncontrolled cell division
2) decreased apoptosis
___ cells most likely the source of tumours.
stem
key cancer characteristics
a) metastasis
b) immortalisation
c) angiogenesis
d) transformation
e) carcinomas
a) development of secondary malignant growths at a distance from a primary site of cancer.
b) indefinite cell growth
c) formation of new blood vessels
d) Malignant transformation is the process by which cells acquire the properties of cancer
e) epithelial cancers
What test is used to test a potentially mutagenic substance?
Ames test
Describe the Ames test
1) choose potential mutagen
2) mix with liver cell extract in order to metabolise the mutagen
3) incubate with Salmonella cells with a reporter trait such as an inability to synthesise its own histidine
4) grown on minimal medium without histidine
5) should see growth and an increased colony count as the mutagen influences DNA
- usually colonies wouldn’t be seen as histidine is not present
What does it mean that the salmonella in the Ames test is ‘sensitised’?
- has defect in DNA repair machinery, so background mutation increases
What is an ocogene?
gene whose normal protein product promotes cell division
What is a tumour suppressor gene?
Mutations are therefore?
gene that produces a protein product that normally suppresses cell promotion or tumorgenesis
- loss of function recessive
What is a transfection assay? Identified what?
searched for DNA sequences inside cells that could provoke uncontrolled proliferation when injected into non-cancerous cell lines
- Ras oncogene that when mutated causes unregulated cell division
How do oncogenes promote cell division? i.e. what happens when they are mutated?
- produces dominant activating mutations
a) what is the significance of the viral oncogene ‘v-src’? Normal version is called (b).
viral version is mutated and hyperactive, creating unregulated host cell division
b) s-src
How do mutated oncogenes function?
- mitogen binds to cell surface receptor which is bound to a intracellular kinase
- downstream of the Ras oncogene is a MAP kinase that is activated by a GTPase
- cascade activates and produces transcription factors leading to uncontrolled cell division
ONCOGENE SUMMARY
Oncogenes were identified using (a) virus studies. They are activated through (b) gain of function mutations. They switch on (c) factor signalling pathways and some even switch off (d).
a) tumour
b) dominant
c) growth
d) apoptosis
What does it mean when we say cancer is a multifactorial disease?
usually a mutation in one oncogene is not enough, a cancer will tend to have a mutation in multiple, distinct oncogenes.
What did cell fusion experiments reveal about the cancer phenotype?
when tumour suppressor cells are fused to normal cells, tumours are not produced
- suggesting the cancer phenotype as a whole is recessive
How does Knudson’s 2 hit hypothesis relate to the function and phenotype of tumour suppressor genes in Retinoblastoma?
b) therefore non-_____
- requires 2 loss of function mutations in Rb
- one comes in the form of a tumour suppressor gene and the second is the loss of heterozygosity
b) hereditary
Retinoblastoma is a recessive (a) cancer. (b) are safe, but are much more likely to get cancer from the mutation of the wild type allele into a (c) allele.
a) eye
b) heterozygotes
c) Rb
How can a second hit occur (loss of heterozygosity)?
1) non-disjunction (chromosome loss)
2) mitotic recombination
3) gene conversion
4) deletion
5) point mutation
What is a cell cycle restriction point?
- a ‘decision’ for a cell to enter cell cycle, determined by a cyclin- D dependent complex
- point at which G1 occurs where cells no longer need growth factors to complete cell cycle
Rb is a __ regulator of E2F (a key transcriptional factor at the restriction point). Meaning?
negative
- the cells usually don’t enter through to G1
What occurs when Rb is active?
E2F is produced and genes are transcribed to allow cell transition to G1
Rb itself is inhibited by what? a)
b) BUT in the presence of what CDK inhibiter means that this component is switched off?
c) leading to what?
a) CDK- 4
b) p16
c) constantly active E2F and inappropriate cell proliferation
What is the function of tumour suppressor p53?
usually a stress sensor and a transcriptional factor- allowing cells to undergo apoptosis, or senescence
- halts cell cycle
What is a mitogen?
a chemical substance that encourages cells to commence cell division, triggering mitosis
