cancer

Question 1

how normal proto-oncogene works

Answer 1

e.g. ras gene
- codes for ras protein
- growth factor (signal molecule)
-> RTK receptor (receptor protein)
-> activate ras protein (G protein) by replacing GDP wit GTP
-> triggers phosphorylation cascade
-> last PK of STP activates transcription of genes encoding proteins that stimulate cell div

Question 2

GOF mutation in proto-oncogene

Answer 2

• Become oncogene
• leading to
  
  • over-expression
  • or hyperactive ras protein
• GTP being bonded to ras protein (as ras-GTP complex) with or w/o growth factor (constant “active” state)
• increase in cell signalling, transcription and consequently stimulation of cell cycle

Question 3

how normal tumour suppressor gene works

Answer 3

e.g. p53 gene
- codes for protein which inhibits uncontrolled cell division
- when there is DNA damage
- arrests cell cycle
- activates DNA repair proteins
- when DNA damage is irreparable
- initiates apoptosis

Question 4

stages in multi-step model of cancer progression

Answer 4

1. Gradual accumulation of several independent mutations in cancer-critical genes in a single cell lineage
2. activation of telomerase
3. angiogenesis
   - tumour cell releases angiogenesis-activating proteins that attract endothelial cells
   - endothelial cells secrete protein-degrading enzymes -> blood vessel walls being broken down
   - thus resulting in the formation of new blood vessels
4. metastasis
   - cancer cells enter circulatory system and travel to distant sites where they form metastases (secondary tumours)

Question 5

importance of angiogenesis

Answer 5

• increased supply of oxygen and nutrients to support cell growth and cell division
• removal of toxic waste products

Question 6

causative factors of cancer

Answer 6

• ionising radiation
  
  • (result in production of free radicals of water)
  • interact with DNA to produce double stranded breaks
  • leading to chromosomal rearrangements and deletion
• polycyclic aromatic hydrocarbons
  in cigarette and tobacco smoke
  
  • binds to DNA to form adducts
  • which causes mistakes in DNA rep
  • leading to gene mutations
• heterocyclic amines in charred mess
  
  • bind to DNA
  • and cause mistakes in DNA rep
  • leading to gene mutations
• inherited mutations in CC genes
• loss of immunity
• viral infections

Question 7

how dysregulation of checkpoints of cell division may occur

Answer 7

• (mutation)
  
  • mutation in CDK gene
  • mutation in cyclin gene
  • mutation in gene that codes for enzyme to breakdown cyclin
• (effects of mutation)
  
  • change in specific 3D conformation of CDK, resulting in formation of hyperactive CDK
  • overproduction of cyclin
  • change in specific 3D conformation of active site of enzyme, resulting in non-functional enzyme which breaks down cyclin
    OR no production of enzyme which breaks down cyclin
• (link to dysregulation)
  
  • more active M-CDK complexes formed
  • CDK continually bound to cyclin

Question 8

how telomerase genes may be disregulated

Answer 8

• counted as cancer-critical genes
• reactivated in cancer cell
• results in an increase in active telomerase which lengthens the telomeres at the end of chromosomes
• thus preventing cell from entering replicative senescence, allowing cell cycle to continue

Question 9

characteristics of cancer cells

Answer 9

• divide uncontrollably (due to loss of regulation of cell cycle)
• lack contact inhibition
• lack anchorage dependence