CANCER

Question 1

2 ways in which cell division can become out of control

Answer 1

1) uncontrolled cell division

2) decreased apoptosis

Question 2

___ cells most likely the source of tumours.

Answer 2

stem

Question 3

key cancer characteristics

a) metastasis
b) immortalisation
c) angiogenesis
d) transformation
e) carcinomas

Answer 3

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

Question 4

What test is used to test a potentially mutagenic substance?

Answer 4

Ames test

Question 5

Describe the Ames test

Answer 5

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

Question 6

What does it mean that the salmonella in the Ames test is ‘sensitised’?

Answer 6

• has defect in DNA repair machinery, so background mutation increases

Question 7

What is an ocogene?

Answer 7

gene whose normal protein product promotes cell division

Question 8

What is a tumour suppressor gene?

Mutations are therefore?

Answer 8

gene that produces a protein product that normally suppresses cell promotion or tumorgenesis

• loss of function recessive

Question 9

What is a transfection assay? Identified what?

Answer 9

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

Question 10

How do oncogenes promote cell division? i.e. what happens when they are mutated?

Answer 10

• produces dominant activating mutations

Question 11

a) what is the significance of the viral oncogene ‘v-src’? Normal version is called (b).

Answer 11

viral version is mutated and hyperactive, creating unregulated host cell division

b) s-src

Question 12

How do mutated oncogenes function?

Answer 12

• 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

Question 13

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).

Answer 13

a) tumour
b) dominant
c) growth
d) apoptosis

Question 14

What does it mean when we say cancer is a multifactorial disease?

Answer 14

usually a mutation in one oncogene is not enough, a cancer will tend to have a mutation in multiple, distinct oncogenes.

Question 15

What did cell fusion experiments reveal about the cancer phenotype?

Answer 15

when tumour suppressor cells are fused to normal cells, tumours are not produced

• suggesting the cancer phenotype as a whole is recessive

Question 16

How does Knudson’s 2 hit hypothesis relate to the function and phenotype of tumour suppressor genes in Retinoblastoma?

b) therefore non-_____

Answer 16

• 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

Question 17

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.

Answer 17

a) eye
b) heterozygotes
c) Rb

Question 18

How can a second hit occur (loss of heterozygosity)?

Answer 18

1) non-disjunction (chromosome loss)
2) mitotic recombination
3) gene conversion
4) deletion
5) point mutation

Question 19

What is a cell cycle restriction point?

Answer 19

• 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

Question 20

Rb is a __ regulator of E2F (a key transcriptional factor at the restriction point). Meaning?

Answer 20

negative

• the cells usually don’t enter through to G1

Question 21

What occurs when Rb is active?

Answer 21

E2F is produced and genes are transcribed to allow cell transition to G1

Question 22

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?

Answer 22

a) CDK- 4
b) p16
c) constantly active E2F and inappropriate cell proliferation

Question 23

What is the function of tumour suppressor p53?

Answer 23

usually a stress sensor and a transcriptional factor- allowing cells to undergo apoptosis, or senescence
- halts cell cycle

Question 24

What is a mitogen?

Answer 24

a chemical substance that encourages cells to commence cell division, triggering mitosis

Question 25

As a result of low DNA damage what occurs?

Answer 25

CDK inhibition by p53 leading to p21 transcription to trigger apoptosis

Question 26

As a result of high DNA damage what occurs?

Answer 26

ability to transcribe BAX and trigger apoptosis

Question 27

What is BAX?

Answer 27

transcribed to open mitochondrial channels and release cytochrome c, triggering apoptosis

Question 28

What regulates p53 levels?

Answer 28

ubiquitin dependent proteolysis, same as cyclin

Question 29

What is the Hayflick limit?

Answer 29

cells usually stop dividing after 25-50 divisions because of telomere shortening which triggers apoptosis.

Question 30

What is escape replicative senescence?

How is this possible?

Answer 30

when cancer cells don’t stop dividing because their telomeres don’t shorten

• high telomerase activity
• alternative recombination based strategy

Question 31

Why is CRISPR so useful here?

Answer 31

turn back on p53 if mutated!