CANCER 😵

Question 1

How is cancer produced

Answer 1

multi-step model caused by accumulation of mutations in cancer-critical genes in a single cell lineage

Question 2

State the characteristics of cancer cells

Answer 2

1. Increased rate of cell division/uncontrolled cell division: absence of growth factors
2. Genome instability and mutations: increased rate of accumulation of mutations
3. Replicative immortality: telomerase reactivated -> able to evade apoptosis
4. Loss of anchorage-dependence replication: able to replicate without attachment to a surface for anchorage indepedent growth
5. Loss of contact inhibition and density-dependent replication: continues to replicate even after coming into contact with neighbouring cells
6. Induces angiogenesis: tumour cells expresses angiogenesis activating protein genes to produce angiogenesis activating proteins -> stimulates angiogenesis, growth of new blood vessles -> increase blood supply to cancer cells:
   * increase supply of nutrients and oxygen to cancer cells and removal of toxic waste materials
   * pathway for cancer cells to spread to other sites in the body
7. Induces metastasis
   * primary tumours penetrate lymphatic and blood vessles, entering blood stream
   * circulatory system transports cancer cells through out body
   * cancer cells leave the blood stream and enter particular organ, form secondary tumours at distant sites from primary tumour
8. Evade immune destruction: some cancer cells able to disable components of the immune system

Question 3

Defintion of angionegenesis

Answer 3

growth of new bloods vessles

Question 4

Definition of metastasis

Answer 4

process in which primary tumours invade local tissue and blood vessels, establishing secondary tumours known as metastases at distant sites from primary tumours

Question 5

What are benign tumours

Answer 5

contain few genetic mutations and do not cause serioud health problems

can be removed by surgery

Question 6

What are malignant tumours

Answer 6

are invasive and could impair function of organs, are cancerous

requires systematic treatment in conjuncation with surgery to ensure complete removal

Question 7

Differences between benign and malignant tumours

Answer 7

Nucleus:
Benign tumour: small nucleus that is regularly shaped
Malignant tumour: large nucleus that is irregularly shaped

Nucleus: Cytoplasmic ratio
Benign tumour: benign tumour cells have low nuclear: cytoplasmic ratio
Malignant tumour: high nuclear:cytoplasmic ratio(aneuploidy/poluploidy)

Rate of mitosis:
Benign tumour: low rate of mitosis due to lower rate of division compared to malignant tumours
Malignant tumour: high rate of mitosis due to rapid division of cells

Question 8

What is a tumour supressor gene and its function

Answer 8

• inhibits uncontrolled cell division
• codes for proteins that prevent uncontrolled cell division
  1. Takes part in cell signalling pathways that inhibit cell cycle
  2. Halts cell division if DNA damaged
  3. Trigger DNA repair mechanisms to prevent cells from accumulating DNA damage
  4. Initiates cell apoptosis when damage is irreparable
  5. Maintains cell-to-cell adhesion

Question 9

What mutation occurs in TSG

Answer 9

1. loss of function mutation: synthesises non-functional protein, unable to regulate cell cycle
2. must be in both copies: if one copy is mutated, other normal copy is able to produce sufficient product to regulate normal cell cycle

Question 10

Function of p53 gene

Answer 10

• transcription factor that binds to DNA to trigger transcription of genes involved in cell cycle inhibition.
• activate DNA repair proteins involved in repair of damaged DNA
• arrest cell cycle
  1. p53 protein binds to specific DNA control elements and promotes transcription of genes involved in cell cycle inhibition, p21 gene
  2. p21 protein binds to protein involved in cell cycle progress, eg. CdKs
• initiates apoptosis

Question 11

What happens when p53 gene is mutated

Answer 11

mutation in coding region:
* 3D conformation of p53 protein altered
* unable to activate expression of gene invovled in cell cycle inhibition
* proteins involved in DNA repair, cell cycle arrest, apoptosis not synthesised
* cell cycle cannot be inhibited, leading to accumulation of mutations in daughter cells

mutation in promoter:
* general transcription factors and RNA polymerase unable to bind to promoter region of p53 gene
* p53 gene not expressed, p53 protein not produced
* unable to activate proteins involved in DNA repair, cell cycle arrest and apopotosis
* unable to carry out inhibition of cell cycle, leading to accumulation of mutations in daughter cells

Question 11

What are protooncogenes

Answer 11

encode gene products that promote normal cell division, usually codes for synthesis of: growth factors, growth factor receptors, protein kinases, transcription factors, inhibitors of apoptosis,

Question 12

What mutations occur in protooncogene

Answer 12

1. gain in function mutation: protooncogenes converted to oncogenes that are over-expressed or hyper active, leading to excessive cell division, causing cell division to be uncontrolled
2. oncogene acts in a dominant manner and only one copy of gene needs to be activated for there to be excessive cell division -> single copy of oncogene able to mask the effect of the normal allele

Question 13

What are ras gene + their function

Answer 13

encode for ras proteins that belong to a family of low-molecular weight G proteins

activation of pathway enables signal from growth factor to be relayed to a series of protein kinases via a phosphorylation cascade, last protein kinase of signal transduction pathway leads to the transcription of a gene encoding for protein that stimulates cell division

Question 14

What happens to ras gene when mutated

Answer 14

in coding region:
* change in 3D conformation of ras protein
* constantly bound to GTP as ras-GTP complex even when growth factor absent
* ras protein always active
* increase cell signall, transcription of genes encoding for proteins that stimulate cell division
* overstimulation of cell cycle, leading to excessive cell division

in promoter region:
* improved recruitment and binding of GTP and RNA pol to promoter of ras gene, increased expression of ras gene
* increase in absolute quantity of ras protein in cells
* increase cell signall and transcription of genes coding for proteins that stimulate cell division
* overstimulation of cell cycle
* excessive cell division

OR chromosal duplication -> increase number of copies of proto-oncogenes -> excess protein OR translocation to an active promoter

Question 15

Multistep model of cancer progression

Answer 15

uncontrolled poliferation of cell leads to unstable genome and accumulation allowing cell to evade normal growth restraints -> activation of telomerase -> angiogenesis -> metastasis

Question 16

What is meant by accumulation of mutations

Answer 16

accumulation of several independent mutations in cancer-critical genes in a single cell lineage

cancer critical genes:
* protooncogene
* tumour suppresor gene
* telomerase gene
* angiongenesis activating protein gene

Question 17

How activation of telomerase leads to cancer

Answer 17

telomorase is a ribonuceloportein that adds telomere repeat sequences of 5’ TTAGGG 3’ to 3’ overhang of DNA

maintaining telomere length after repeated rounds of DNA replication during cell division, prevents cell from hitting Hayflick limit and going into period of cell senescence, cell divide indefinitely and evade cell apoptosis

Question 18

How does angiogenesis contribute to cancer

Answer 18

release angiogenesis activating proteins that recruit endothelial cells and promotes their proliferation

endothelial cells releases protein degrading enzyme called matrix metalloprotein which breaks down blood vessel walls and extracellular matrix, allowing for endothelial cells to become organised to form new network of blood vessels

increases blood supply to tumour, increasing supply of nutrients and oxygens to cancer cells, increase removal of toxic waste products

allow for rapid growth of tumour, while depleting resources from normal healthy cells

Question 19

How does metastasis contribute to cancer

Answer 19

cancer cells invade surrounding tissues and penetrate through walls of lymphatic and blood vessles, entering bloodstream

circulatory system transports cancer cells throughout body

cancer cells exit bloodstream and enter particular organs, forming secondary tumours (metastases) at distant sites from primary tumours

Question 20

List the causes of cancer

Answer 20

Cigarette smoke:
* contains polycyclic aromatic hydrocarbons that binds to DNA and forms adducts, damaging DNA possibly at cancer critical genes
* high likelihood of adducts forming at DNA in lung cells in smokers

UV: excess exposure to UV causes DNA damaging UV B rays to forms covalent attachments between thymine dimers, base substitution, insertion, deletion at cancer critical genes

Ionising radiation(γ-rays and X-rays):
* from nuclear explosions or medical diagnosis
* causes double stranded breaks in DNA leading to chromosal rearrangement and deletion

Genetic predisposition:
* inherits a copy of mutated TSG or oncogene leads to individual to be predisposed with higher chance of developing cancer as they are able to accumulate the necessary mutations in a shorter period of time

Decreased immunity:
* consumption of immune system suppressor drugs that decreases immunity, decreasing cell counts of white blood cells such as helper T and cytotoxic T cells
* decrease ability of helper T cells to detect cancer cells
* decrease ability of cytotoxic T cells to destroy cancer cells

Tumour viruses: integrates genetic material into cellular DNA
* inactives TSG or converts protooncogenes to oncogenes
* direct synthesis of viral proteins that deactivate p53 and other TSG
* insertion of oncogene into normal DNA