book 5 (cancer)

Question 1

explain the significance of the mitotic cell cycle & the need to regulate it tightly

Answer 1

1. cell cycle checkpoints regulate the cell cycle progression and regulates cell division
2. the mutations in genes controlling cell cycle may lead to cell cycle progression
3. dysregulation in cell cycle signalling pathway may also lead to cell cycle progression
4. dysregulation of G1 checkpoint may result in DNA replication of defective DNA
5. dysregulation of G2 checkpoint may result in cell cycle progression despite DNA damage during DNA replication and also results in cells escaping apoptosis even if there is irreparable damage
6. dysregulation of M checkpoint may result in cell cycle progression even if there is non-disjunction
7. gene mutations or chromosomal aberrations are passed down to daughter cells as the cells do not stop dividing to repair damage
8. successive rounds of cell division allows accumulation of mutations in other cancer critical genes such as ras or p53 genes in a single cell lineage
9. eventually there is uncontrolled cell division as the rate of cell division is greater than that of cell death, leading to cancer

Question 2

state the causative factors which can increase chances of cancerous growth

Answer 2

1. genetic - inheriting oncogenes and / or faulty copies of tumour suppressor genes from parents
2. chemical carcinogens such as tar in cigarettes
3. ionizing radiation such as UV lights
4. loss of immunity - the loss of immune system compromising of T-cells and B-cells that can defect and destroy cancerous cells

Question 3

state the functions of proto-oncogenes

Answer 3

1. they are genes whose products promote cell division and cell growth
2. it codes for transcription factors that stimulate the expression of other genes
3. it codes for signal transduction molecules that indirectly stimulate cell division
4. codes for cell cycle regulators

Question 4

explain how the gain in function mutation of proto-oncogenes, including ras, results in uncontrolled cell division

Answer 4

1. gain of function mutation of proto-oncogene to form oncogene which behaves as dominant alleles whereby only one mutated allele is required to produce an abnormal protein, which is:
   - constitutively active
   - binds to it’s substrates with increase affinity
   - degradation-resistant
   thus leading to the over-stimulation of the cell cycle

Question 5

state the function of tumour-suppressor genes

Answer 5

1. they are genes whose protein products inhibit cell division during DNA damage and help prevent inappropriate cell cycle progression
2. the genes codes for transcription factors that repress or stimulate transcription of other genes that codes for p53 tumour suppressor protein which results in:
   - arrest of cell division - allows for more time for DNA repair
   - results in apoptosis and programmed cell death

Question 6

explain how the loss of function of tumour suppressor genes, including p53, results in uncontrolled cell division

Answer 6

1. loss of function mutation of tumour suppressor gene whereby mutated tumour suppressor allele behaves like recessive alleles, both alleles must be mutated to produce an abnormal and non-functional tumour suppressor protein which:
   - cannot activate certain genes to arrest cell division, leading to loss of arrest of cell division
   - loss of ability for DNA repair
   - loss of apoptosis during DNA damage
   results in the loss of control of cell cycle and inappropriate cell cycle progression

Question 7

describe the development of cancer as a multi-step process

Answer 7

1. loss of function mutation of tumour suppressor gene whereby the mutant tumour suppressor alleles behave like recessive alleles, 2 alleles must be mutates to produce an abnormal and non-functional protein.
2. this leads to the loss of arrest of cell division, the loss of ability for DNA repair and loss of apoptosis
3. the gain of function mutation of proto-oncogene to form oncogene which behaves as dominant alleles whereby only one mutated allele is required to produce an abnormal protein
4. this leads to the stimulation of cell cycle - cell keeps dividing
5. these leads to the accumulation of many mutations
6. activation of telomerase gene - telomerase enzyme prevents the shortening of chromosome ends, allowing the cell to continue to divide indefinitely
7. the loss of ability to differentiate
8. cells no longer exhibit anchorage dependence - the loss of cell adhesion
9. loss of density-dependence - cells do not stop dividing to form a benign tumour
10. angiogenesis can occur - the formation of new network of blood vessels to the cancer cells which provides cancer cells with nutrients and oxygen for growth and to also remove any waste products
11. metastasis can occur - cancer cells can detach from the parent mass, invade surrounding tissues and spread via the circulatory system to other tissues to form secondary tumours
12. tumour is now malignant