Week 4: Signalling transduction in cancer

Question 1

Function of Tumour Suppressors

Answer 1

Encodes for proteins that can:
- Sense DNA damage or inappropriate growth/signals
- Act to arrest proliferation or induce apoptosis
- Monitor:
+ Cell cycle checkpoints
+ Apoptosis
+ DNA repair
+ Transcription
+ Differentiation
+ Activation of signalling apthways involved in growth stimulation

Question 2

Familial Cancer Syndromes

Answer 2

Inherited genetic mutations that predispose people to cancer development, but this doesn’t mean that all cells with this mutation will cause cancer, but this is something that we are still learning

Question 3

Tumour Suppressors vs Oncogenes: How to initiate cancer?

Answer 3

In theory, since oncogenes are dominant whilst tumour suppressors are recessive, meaning that they require 2 copies to be functional, both tumour suppressor genes must be inactivated, silenced or mutated to cause cancer, also known as Knudson’s 2-hit hypothesis

Question 4

p53: “Guardian of the genome”

Answer 4

• One of the most commonly mutated genes in cancers, but despite all the research we have done, we still don’t really have a good understanding of what it does exactly
• A tumour suppressor in every cell type, a multi-domain transcription factor, binds as a tetramer to regulate gene expression at gene regulatory sites
• Can be activated by a range of upstream signals that lead to a range of downstream effects
• Different mutations in p53 yields different results

Question 5

p53 upstream signals

Answer 5

• Lack of nucleotides
• UV nucleotides
• Ionising radiation
• Oncogene signaling
• Hypoxia
• Blockage of transcription

Question 6

p53 downstream effects

Answer 6

• Cell cycle arrest, leading to cell senescence or return to proliferation
• DNA repair
• Block of angiogenesis
• Apoptosis

Question 7

pRb (Retinoblastoma)

Answer 7

• Either sporadic or familial, mostly unilateral tumours and bilateral tumours respectively
• Familail Rb people carry 1 mutated copy of pRb
• Rb mutations are seen in 1:20,000 children
• Hereditary forms are usually diagnosed between birth + 6-8 years of age
  -Rb is inherited as a dominant trait, but recessive at the cellular level