Cancer 1

Question 1

What is cancer characterised by

Answer 1

Unregulated growth facilitated by mutations in cell cycle regulations

Question 2

What is meant by the term metastatic?

Answer 2

Characteristic of of malignant tumours allowing them to spread

Question 3

What are adenocarcinomas?

Answer 3

Arise from secretary epithelial cells

Question 4

What are the names of tumours that arise from epithelial cells?

Answer 4

Carcinoma’s

Question 5

What does the protective layer of epithelial cells give rise to?

Answer 5

Squamous carcinoma’s

Question 6

Why do cells in females tumour’s have the same inactive X chromosome?

Answer 6

Because all cells in tumour are derived from single progenitor cells and only one single cell is transformed into cancer cell and cloned to get all of the others

Question 7

What are the 6 hallmarks of cancer?

Answer 7

1. Resisting cell death
2. Sustain proliferation signalling
3. Evading growth suppressors
4. Activating invasion and metastasis
5. Enabling replicative immortality
6. Inducing angiogenesis

Question 8

What can enhanced external stimulation of sustained proliferation do to receptors?

Answer 8

Dysregulate them as there is so much growth

Question 9

What are 3 ways growth signalling autonomy to maintain proliferation can be achieved?

Answer 9

1. Mutations in GF receptors - so permanently active therefore kinase is permanently active and signals downstream
2. Receptor and level of GF could be normal but have active mutations in key molecules in signalling pathway e.g. PI3-kinase, Ras & Raf
3. Mutations in molecules involved in cell cycle

Question 10

How do cancer cells ‘avoid’ growth inhibiting signals?

Answer 10

Have loss of activity of tumour suppressor genes i.e. p53, PTEN & Retinoblastoma (Rb). And through aberration of TGF-Beta antiproliferative gene (change to its structure)

Question 11

What are the consequences of PTEN not being activated?

Answer 11

Causes upregulation of Akt-signalling which is very powerful in enhancing cell survival

Question 12

What does normal PTEN do?

Answer 12

It’s a lipid phosphatase that normally dephosphorylates PIP3 to PIP2

Question 13

What is the purpose of apoptosis?

Answer 13

To get rid of all the damaged cells essential to maintain DNA fidelity

Question 14

How do cancer cells avoid apoptosis?

Answer 14

Mutations in molecules affecting intrinsic pathway - loss of p53, upregulation of anti-apoptotic members of BCL-2 family and down-regulation of pro-apoptotic BCL-2 family members.
And mutations in the extrinsic pathway

Question 15

Where/ when does angiogenesis normally occur?

Answer 15

Embryonic growth, adolescence, female reproductive organs and wound healing

Question 16

How does angiogenesis occur in tumour growth?

Answer 16

Areas of tumours become hypoxic so require vascularisation and develops its own blood supply.
Tumour will tip balance in favour of molecules that produce angiogenesis

Question 17

What is the rate limiting step in tumour growth?

Answer 17

Angiogenesis

Question 18

What is the key molecule implicated in angiogenesis?

Answer 18

VEGF - essential for tumour angiogenesis (vascular endothelial growth factors)

Question 19

What is different about the blood vessels produced in tumours compared to healthy blood vessels?

Answer 19

Abnormal, leak and don’t have a hierarchy - as in no difference between capillary/ artery etc.

Question 20

How is VEGF expression upregulated?

Answer 20

By hypoxia and over-activation of other growth factor signalling pathways

Question 21

What happens in the tumour when areas of it become hypoxic? (5 marks)

Answer 21

• It induces signalling to tumour to make VEGF.
• VEGF binds to its receptor = dimerization.
• Activates a kinase which adds phosphate to the opposite receptor this is known as autophosphorylation.
• After autophosphorylation, proteins containing SH2 domain bind to the phosphorylated receptor and trigger activation of Ras & Raf-MEK-MAPK cascade
• PI3K is also activated and AKT signalling takes place

Question 22

How is Akt signalling used to promote angiogenesis?

Answer 22

Leads to the inhibition of apoptosis and stimulates endothelial NO synthase and stimulates vascular permeability via NO production

Question 23

What helps the dilation of blood vessels in angiogenesis?

Answer 23

Nitric oxide - blood vessels need to dilate in order for new ones to spring from it

Question 24

What is a telomere?

Answer 24

Repetitive DNA sample found on the end of chromosomes and act a a molecular counter

Question 25

What happens to telomere’s normally in replication?

Answer 25

With each round of replication telomere’s shorten and eventually die by apoptosis due to their limit of a DNA polymerase primer.

Primer is removed after replication in the 3-5 end so its not copied and will be unstable

Question 26

How do stem cells maintain telomere length?

Answer 26

Using reverse transcriptase which has a RNA template for telomere replicative sequence and maintains telomere length

Question 27

How do cancer cells hijack telomerase?

Answer 27

Increase TTAGGG and stop telomere from shortening and extend it. This makes the chromosome unstable and facilitates ability of chromosomes to precure more mutations