Cancer

Define cancer

1. Cancer is the disease characterised by uncontrolled cell division.

2. It is due to the failure of cells to control cell division and or undergo apoptosis.

Distinguish between benign and malignant tumours

1. Benign tumours are not cancerous while malignant tumours are made up of cancerous cells.

2. Benign tumours usually grow quite slowly while malignant tumours grow faster than benign tumours.

3. Benign tumours do not spread to other parts of the body while malignant tumour cells are able to metastasise by entering the bloodstream and invade other tissues.

State the various characteristics of cancer cells

1. Cancer cells do not stop dividing. Telomeres of their chromosomes do not shorten with each round of cell division.

2. Cancer cells do not become specialised. They remain undifferentiated so that mitotic cell division continues.

3. Cancer cells do not undergo apoptosis.

4. Cancer cells are anchorage independent. This feature is important for cancer metastasis.

5. Cancer cells do not exhibit density-dependent inhibition. The cells continue dividing and growing over adjacent cells in disordered, multi-layered patterns.

6. Cancer cells can stimulate the growth of blood vessels towards themselves (angiogenesis) to obtain the necessary oxygen and nutrients they need to thrive and allow for metastasis of cancer cells.

Explain how a secondary tumour can develop from a primary tumour

1. Cancer cells of primary tumours can stimulate the growth of blood vessels towards themselves (angiogenesis) to obtain the necessary oxygen and nutrients they need to thrive and allow for metastasis of cancer cells.

2. Cancer cells of primary tumours can enter the blood or lymphatic system, travel through the bloodstream and invade normal tissues elsewhere in the body.

3. The cells divide controllably. This forms a new tumour at the new site of the body.

Describe the various functions of cell cycle checkpoints

1. To ensure that proper conditions in a cell are achieved before proceeding to the next stage of the cell cycle or the completion of cell division.

2. To ensure that incomplete or damaged DNA are not replicated and not passed on to daughter cells.

3. Allows the cell cycle to be regulated by extracellular signals from other cells.

Describe how dysregulation of cell cycle checkpoints may lead to cancer

1. Dysregulation of cell cycle checkpoints leads to uncontrolled cell division.

2. Checkpoints ensure that proper conditions in a cell are achieved before proceeding to the next stage of the cell cycle or the completion of cell division.

3. During the G1 checkpoint, the cell checks for DNA damage before proceeding to S phase where DNA is replicated. When unregulated, DNA with mutations are replicated and passed to daughter cells after mitosis.

4. During the G2 checkpoint, the cell checks that DNA replication is completed and there is no DNA damage. When unregulated, cells with mutations are allowed to complete mitosis.

5. During the G3 checkpoint, the cell checks for correct attachment of chromosomes to spindle fibres during metaphase. When unregulated, chromosome aberrations occur and daughter cells receive an incomplete set of chromosomes.

6. As such, mutations of several proto-oncogenes and tumour suppressor genes may accumulate in a single cell.

Describe the function of cyclins

1. Cyclins are regulatory proteins whose concentration rises and falls as the cell goes through the cell cycle.

2. Their varying concentrations are due to their formation or degradation at different phases of the cell cycle.

3. They activate protein kinases.

Describe the function of cyclin-dependent kinases

1. Cyclin-dependent kinase is an enzyme that phosphorylates and hence activate target proteins in the cell.

2. They are activated when attached to cyclin.

3. They are inactivated when cyclin is degraded.

Define proto-oncogenes

1. Proto-oncogenes are normal genes which code for proteins (growth factors, growth factor receptors, any factors in a cell signalling pathway and transcription factors) that stimulate normal cell division.

2. Proto-oncogenes become mutated due to a gain in function mutation to become oncogenes.

Define oncogenes

1. Oncogene genes are the mutated form of proto-oncogenes which code for proteins that stimulate uncontrolled cell division.

2. Oncogene is a dominant allele as the gain in function mutation in a single copy of the gene is sufficient for the mutant phenotype to be expressed.

Describe the various ways gain in function mutation can occur

1. Over-expression of the gene. This results in the excessive production of the gene product.

2. The gene product (ras protein) is hyperactive or resistant to degradation.

3. Gain in function mutation results in a dominant allele as the gain in function mutation in a single copy of the gene is sufficient for the mutant phenotype to be expressed.

Describe the various ways proto-oncogenes undergo gain in function mutation to become oncogenes

1. Chromosomal translocation. A gene is transferred to a different location on the same chromosome or different chromosome such that it is close to a regulatory sequence or strong promoter. This results in the excessive production of the normal protein. Hence, cells divide excessively.

2. Gene amplification. Errors in DNA replication may result in extra copies of the proto-oncogene. This results in the excessive production of the normal protein. Hence, cells divide excessively.

3. Mutation in the DNA coding sequence results in a protein that is hyperactive or resistant to degradation. It constantly stimulates cell division. Hence, cells divide excessively.

Describe the function of Ras protein

1. ras gene codes for Ras protein which stimulates normal cell division.

2. Ras protein is a G protein which is part of a cell signalling pathway involved in stimulating normal cell division.

Describe the various features of a normal Ras protein

1. It is a G protein.

2. It is activated when bound to GTP.

3. It is inactivated when bound to GDP.

4. When a growth factor binds to the cell surface receptor, Ras protein is activated by GTP which replaces the bound GDP on the Ras protein.

5. Ras protein contains enzyme GTPase which hydrolyses the bound GTP to GDP.

6. This returns the Ras protein to its inactive state.

Describe how a gain in function mutation of the ras gene affects GTPase activity of the Ras protein

1. The gain in function mutation changes the DNA nucleotide sequence.

2. This changes the sequence of codons on mRNA upon transcription.

3. This changes the sequence of amino acids (contact or catalytic amino acid changed to different amino acids with different R groups) on polypeptide upon translation.

4. This affects the secondary and tertiary structures of the protein. This affects the 3D conformation of enzyme GTPase active site such that it is no longer complementary to shape of substrate GTP.

5. Enzyme-substrate complex cannot form.

6. It is unable to hydrolyse GTP to GDP.

7. It is non-functional.

8. Ras protein is still associated with GTP and becomes hyperactive.

Define tumour suppressor genes

1. Tumour suppressor genes are normal genes which code for proteins that inhibit the cell cycle and may initate apoptosis.

2. Tumour suppressor genes become mutated due to a loss of function mutation to become non-functional tumour suppressor genes.

3. Loss of function mutation results in a recessive allele as loss of function mutation in both copies of the gene is required for the mutant phenotype to be expressed.

Describe the various ways tumour suppressor genes undergo loss of function mutation to become non-functional tumour suppressor genes

1. Chromosomal deletion where the gene is found.

2. Mutation in the DNA coding sequence of the gene.

3. Promoter region of the gene may become methylated hence the gene is not expressed.

4. The gene is packed in the heterochromatin region hence the gene is not expressed.

Describe how p53 protein controls the cell cycle

1. At G1 checkpoint of the cell cycle, p53 protein monitors the integrity of DNA by checking for DNA damage and length of telomeres of chromosomes.

2. If it detects damaged DNA or telomeres are too short, it stops cell division by preventing the cell from entering S phase.

3. This prevents damaged DNA from being replicated.

4. p53 protein also acts as a transcription factor for several genes. It activates the transcription of several genes to produce special DNA repair enzymes to repair damaged DNA.

5. Once DNA is repaired, p53 protein allows cell division to proceed.

Describe how p53 initiates apoptosis

1. If damaged DNA cannot be repaired, p53 protein initiates apoptosis by activating genes involved in apoptosis.

2. This results in cell death.

Describe how p53 protein maintains genetic stability

1. p53 protein ensures that daughter cells are genetically identical to parent cells.

2. When p53 is non-functional, cancer cells can repeatedly undergo cell division without being stopped at the G1 checkpoint.

3. The genetically damaged cells replicate its DNA and pass mutations to its daughter cells.

4. The mutations will accumulate.

5. The mutated daughter cells escape apoptosis and continue dividing to produce new cells with damaged DNA which are genetically unstable and will lead to further mutations.

Distinguish between proto-oncogenes and tumour suppressor genes

1. Proto-oncogenes code for proteins which stimulate normal cell growth and division while tumour suppressor genes code for proteins which inhibit the cell cycle and may trigger apoptosis.

2. Proto-oncogenes undergo gain in function mutation to become oncogenes while tumour suppressor genes undergo loss of function mutation to become non-functional tumour suppressor genes.

3. For proto-oncogenes, the mutated allele codes for proteins which stimulate uncontrolled cell growth and division while for tumour suppressor genes, the mutated allele codes for non-functional proteins which are unable to inhibit the cell cycle nor trigger apoptosis.

Explain how one named intrinsic factor and one named extrinsic factor can increase the chances of a cancerous growth

1. Tar in cigarette smoke has a detrimental effect on the structure of DNA and is likely to cause mutations in genes.

2. Individuals with low immunity have to take drugs to suppress their immune systems to stop organ rejection.

3. It takes time for many mutations to accumulate in a single cell before it becomes cancerous.

4. Several independent mutations must be present in a single cell.

5. Gain in function mutation of at least one proto-oncogene to oncogene. When one allele of each proto-oncogene is mutated, cells divide uncontrollably.

6. Loss of function mutation in several tumour suppressor genes.

7. When both alleles of each tumour suppressor gene are mutated, the protein formed is non-functional and is unable to inhibit the cell cycle nor initiate apoptosis.

8. Activation of enzyme telomerase gene.

9. Telomerase catalyses the lengthening of telomeres.

10. This allows cancer cells to divide uncontrollably without triggering apoptosis as telomeres do not shorten to a critical length.