Cancer Biology

Question 1

Changes in the cell causing cancer

Answer 1

Nucleus becomes bigger, more disoranged arrangement, RNA builds up, loss of differentiate features (anaplasia)

Question 2

Explain the multistep process of tumourigenesis resulting from the accumulation of mutations

Answer 2

Cells aquire mutations over many years causing an accumulation of genetic mutations.
1. Initiation: often due to environmental changes causing mutations
2. Accumulation of mutations: activation of oncogenes, loss of tumour suppressors
3. Proliferation and further mutations
4. One cell passes threshold to malignancy

Question 3

Definition of proto-oncogenes and tumour suppressors, Functions of proto-oncogenes and tumour suppressor genes in normal cells. Examples for each:

Answer 3

Proteo-oncogene Definition: a normal gene that if mutated gives rise to oncogene
Function: codes for proteins involved in regulation
Examples: receptors (EGFR, HER2, c-Met), cytoplastmic signalling intermediates (Ras, BRAF, other kinases), Nuclear proteins/ transcription factors (e.g. Myc)
Tumour suppressor Definition/ function: gene coding for a protein which directly or indirectly inhibits progression through cell cycle
Example: RB, p53, BRCA1

Question 4

How do mutations lead to activation of proto-oncogenes?

Answer 4

Deletion/ point mutations: hyperactive protein in normal amounts (e.g. RAS, BRAF, EGFR)
Regulatory muation: normal protein but overproduced
Gene amplification: overproduction of normal protein (e.g. ERB B2)
Chromosome rearrangement: protein over produced or overactive fusion protein produced (e.g. bcr-abl gene)

Question 5

How does proto-oncogene activation and loss of tsgs lead to cancer?

Answer 5

Mutation of proto-ocnocgenes causes them to become cancerous (an oncogene). Oncogenes tend to be dominant and encode proteins that stimulate cell division, inhibit cell differentiation and halt cell death.
Tumour suppressor genes normally function to inhibit cell proliferation and tumour development. Loss or inactivation of these genes removes the negative regulators of cell proliferation and contribute to abnormal proliferation of tumour cells.

Question 6

What are the 6 charachteristics of cancer? Breifly describe each:

Answer 6

1. Self sufficiency in growth factors: cancer cells gain autonomous drive to proliferate as molecules initiating proliferation switched on
2. Insensitivity to growth-inhibitory factors: inactivation of tumour suppressor genes normally inhibiting growth
3. Evasion of apoptosis: suppress and inactivation of genes enabling cell death
4. Limitless replication potential: overexpression of telomerase prevents telomeres shortening
5. Sustained angiogenesis: able to gain blood supply to tumour by releasing VEGF which causes blood vessels to grow towards it
6. Tissue invasion and metastisis: able to migrate to other organs, invade other tissues and colonise organs

Question 7

What molecular changes allow a tumour cell to metastisise?

Answer 7

• Defective adherins junctions
• Production of proteases especially MMPs such as collagenase which invade through basement membrane allowing spread to blood and lymphatic vessels

Question 8

What are three catagories of proto-oncogenes?
Give examples for each:

Answer 8

Receptors: EGFR, HER2, c-Met
Cytoplasmic signalling intermediates: Ras, BRAF, other kinases
Nuclear proteins/ transcription factors: myc

Question 9

What are 3 example of tumour suppressor genes?

Answer 9

p53, RB, BRCA1