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SSC- Biology of Cancer > Tumour Suppressors > Flashcards

Flashcards in Tumour Suppressors Deck (63)
1

What is a tumour suppressor gene? 

A gene that protects the cell from one or more steps on the path to cancer. 

A gene which, when mutated, predisposes an individual to cancer 

2

What are the different classifications for tumour suppressor genes? 

  • Gatekeepers
  • Caretakers
  • Landscapers

 

3

What do gatekeeper tumour supressor genes do? 

Prevent growth of potential cancer cells 

4

What do caretaker tumour suppressor genes do? 

Maintain the integrity of the genome 

5

What does failure of the caretaker tumour suppressor genes lead to? 

Genetic instability, which is one of the hallmarks of cancer 

6

What do landscaper tumour suppressor genes do? 

Control the cellular microenvironment 

7

Why is the cellular microenvironment important in cancer? 

Cells around can have a positive or negative effect on cancers . 

8

Which of the hallmarks of cancer do tumour suppressor genes stop? 

  • Deregulating cellular energetics
  • Sustaining proliferative signalling
  • Evading growth suppressors
  • Tumour-promoting inflammation
  • Activating invasion and metastasis
  • Inducing angiogenesis
  • Genome instability and mutation

 

9

What hallmarks of cancer do tumour suppressor genes encourage? 

  • Avoiding immune destruction
  • Enabling replicative immortality
  • Resisting cell death

 

10

What are the two types of retinoblastomas? 

  • Sporadic (60%)
  • Familial (40%)

 

11

How do sporadic and familial retinoblastomas differ? 

  • Familial retinoblastomas appear at a younger age
  • Familial retinoblastomas often develop in both eyes, and can be accompanied by tumours in both organs 

 

12

What can be deduced from the differences between sporadic and familial retinoblastomas? 

Something predisposes the familial patients to cancer

13

What is Knudson's two hit hypothesis? 

That cancer is a multi-hit disease. 

In the case of familial retinoblastoma, one hit is hereditary, and one is acquired

 

 

14

What are the mechanisms for loss of heterozygosity (the second hit)? 

  • Non-disjunction (chromosome loss)
  • Nondisjunction and duplication
  • Mitotic recombination
  • Gene conversion
  • Deletion
  • Point mutation
  • Promoter methylation

 

15

What are human tumour supressor genes normally involved in? 

Cell cycle and DNA damage control 

16

How was p53 originally identified? 

By interactions with viral proteins

17

Which viral proteins did p53 interact with, leading to its initial discovery? 

  • Large T antigen of SV40
  • E1B of adenovirus
  • E6 of papillomavirus 

 

18

What was p53 first thought to be? 

An oncogene

19

In what % of human cancers is p53 mutated? 

50%

20

What must be true of cancer cells that do not have mutated p53? 

p53 must have undergone some form of inactivation 

21

What is Li-Fraumeni syndrome? 

A rare, dominant-inherited cancer syndrome where patients have germline mutation in TP53 

22

What kind of protein is p53?

A nuclear phosphoprotein

23

What is meant by a nuclear phosphoprotein? 

Nuclear - found in nucleus

Phosphoprotein - regulated by phosphorylation 

24

What is the function of p53? 

It is a transcription factor

25

In what form does p53 act? 

In its tetrameric form 

26

How does p53 act as a transcription factor? 

It recognises a 10bp consesus sequence in promoters

27

Where in the molecule do p53 mutations occur? 

They are clustered in exons 5-8

Amino acids 175, 248, and 273 are hotspots 

 

 

28

Describe the expression of p53? 

It is expressed at very low levels in the absense of damage 

29

What is the half life of p53? 

20 minutes 

30

What is the role of p53? 

  • Main role is to define the cellular response to differnet kinds of damage 
  • Has many other dunctions, both in response to stress and in normal conditions - some of these functions are antagonistic and simultaneous

 

 

31

Do the functions of p53 require the transcription of genes? 

Some do (transactivation), some do not 

32

Where do the functions of p53 occur? 

Some in the nucleus, some in the cytosol 

33

What kinds of stress does p53 protect against? 

  • Lack of nucleotides
  • UV radiation
  • Ionising radiation
  • Oncogene signalling
  • Hypoxia
  • Blockage of transcription

 

34

What actions can p53 take to ensure the integrity of the genome? 

  • Cell cycle arrest
  • DNA repair
  • Block of angiogensis
  • Apoptosis

 

35

What can happen to the cell after p53 has induced cell cycle arrest? 

  • Senescence
  • Return to proliferation 

 

36

What is senescence?

Pernament cell arrest

37

How is p53 activated? 

Post-translational modifications 

38

How is p53 activated? 

p53 induces mdm2, which then blocks p53 

39

What are the cellular responses to p53 induction? 

  • Apoptosis
  • Cell cycle arrest, and senescence if prolonged
  • DNA repair
  • Antiangiogenesis
  • Metabolism
  • Pro-survival (goes against other functions)

 

40

What genes are involved in the p53 apoptotic pathways? 

  • Bax
  • PUMA
  • Noxa
  • PERP
  • Fas

 

 

41

What genes are involved in p53 induced cell cycle arrest and sensecence? 

  • p21
  • GADD45
  • Reprimo 

 

42

How do basal levels of p53 act to aid survival? 

They are an anti-oxidant 

43

What is the Warburg effect? 

Cancer cells mostly use aerobic glycolysis to obtain energy, instead of oxphos pathway

44

What kind of energy production do normal cells use? 

  • Oxidative phosphorylation
  • Fatty acid oxidation

 

45

What kind of energy production does p53 induce? 

  • Glycolysis
  • Fatty acid oxidation
  • Oxidative phosphorylation

 

46

What are the types of senescence? 

  • Replicative senescence
  • Stress-induced premature sensecence 

 

47

What causes replicative senesence? 

Short or damaged telomeres

48

What causes stress-induced premature senescence? 

  • Oxidative stress
  • Activated oncogenes
  • Other stresses

 

49

What are telomeres? 

Repetitive DNA sequences that cap the chromosomes and protects their ends from erosion

50

What happens to the telomeres with each duplication? 

Their ends shorten because duplication is not complete

51

What effect does telomerase have on telomeres? 

They elongate them 

52

What kind of cells possess telomerase? 

  • Cancer cells
  • Stem cells

 

 

53

Draw a diagram illustrating the pathway to senesence

54

What is the problem with the accumulation of senescent cells?

They disrupt the tissues and so decrease function 

55

What is antagonistic pleiotrophy? 

When one gene controls more than one phenotypic trait in an organism (pleitropy), at least one of them is beneficial, and at least one is detrimental to the organisms fitness

56

What is PTEN? 

A tumour suppressor with phosphatase activity

57

What does PTEN do? 

Dephosphorylates PIP3,, and so blocks cell proliferation

58

What is PIP3?

A signalling molecular of many pro-growth pathways

59

Where is the PI3K/PTEN pathway commonly inactivated/downregulated? 

In many cancers - prostate, lung, brain 

60

What can induce PTEN? 

p53

61

What does p53 and PTEN together lead to? 

Apoptosis

62

What does p53 without PTEN lead to? 

Senescence

63