Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

L2 Stem Cells > Tumour suppressor genes > Flashcards

Tumour suppressor genes Flashcards

1
Q

Are viral oncogenes dominant or recessive? (2)

A
  • Dominant
  • The normal cell features are recessive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Is the cancer phenotype dominant or recessive?

A

Recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the cell fusion technique? (3)

A
  • Technique to determine whether a phenotype is dominant or recessive
  • Fuse 2 cells of different phenotypes with a fusing agent to form a hybrid cell
  • The phenotype of the hybrid cell will be the dominant phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the fusing agent used in the cell fusion technique?

A

Sendai virus or PEG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the hybrid cell called in the cell fusion technique?

A

Heterokaryon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens when you fuse a cancer cell with a normal cell using the cell fusion technique? (3)

A
  • Inject hybrid cell into a mouse = no tumour is formed
  • This means that the cancer phenotype is recessive
  • Indicates that normal cells carry tumour suppressor genes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the argument in favour of tumour suppressor genes?

A

It is easier to lose the function of a tumour suppressor gene than acquire the specific mutation required to activate an oncogene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the argument against tumour suppressor genes?

A

2 copies of the tumour suppressor gene must be lost to completely lose the function which seems improbable in a short period of time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is retinoblastoma?

A

Tumour in the retina originating from retinoblasts which usually stop growing during embryogenesis and differentiate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are retinoblasts?

A

Precursor of photoreceptor cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the 2 forms of retinoblastoma?

A
  • Sporadic
  • Familial
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the sporadic form of retinoblastoma? (2)

A
  • Occurs in children with no family history of retinoblastoma
  • Causes a single tumour in one eye (unilateral retinoblastoma)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the familial form of retinoblastoma? (2)

A
  • Occurs in children with a parent who suffered from retinoblastoma
  • Causes multiple foci of tumours in both eyes (bilateral retinoblastoma) and increased risk of developing other tumours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Is retinoblastoma dominant or recessive?

A

Recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Knudson’s 1 hit/2 hits hypothesis for retinoblastoma? (3)

A
  • Rate of diagnosis of bilateral retinoblastoma is consistent with a 1 hit model
  • Unilateral retinoblastoma is consistent with a 2 hit model
  • A single event is required to acquire bilateral retinoblastoma but 2 events are required to acquire unilateral retinoblastoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the 1 hit model?

A

A single random event is required to acquire the disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the 2 hit model?

A

2 random and independent events are required to acquire the disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Which form of retinoblastoma is more severe?

A

Bilateral (familial)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What causes retinoblastoma?

A

Loss of function of Rb gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does familial (bilateral) retinoblastoma develop? (3)

A
  • Child inherits one wildtype Rb and one non-functional Rb
  • Only one ‘hit’ is required to take out the wildtype Rb allele, resulting in no functional Rb
  • One mutation is enough to drive bilateral retinoblastoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does sporadic (unilateral) retinoblastoma develop? (3)

A
  • Child inherits 2 wildtype copies of Rb
  • A first mutation doesn’t cause disease because there is still one functional allele
  • Second random mutation results in no functional Rb and unilateral retinoblastoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What kind of gene is Rb?

A

Tumour suppressor gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the probability of 2 random mutations knocking out both copies of the Rb allele in sporadic retinoblastoma?

A

Very very low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is a more likely cause of sporadic retinoblastoma than 2 random mutations? (3)

A
  • Mitotic recombination
  • Causes loss of heterozygosity without any further mutations
  • This process is more frequent than random mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is mitotic recombination in retinoblastoma? (4)

A
  • Cell starts heterozygous for non-functional Rb
  • DNA is replicated
  • Recombination occurs which transfers a copy of mutant Rb onto the normal chromosome so now both chromosomes carry a mutant Rb allele
  • Can result in a loss of heterozygosity in the daughter cells where a daughter cell is left with no functional Rb
26
Q

What are the 2 main mechanisms of stopping cancer development?

A
  • Direct suppression of cell proliferation in response to growth-inhibitory and differentiation-inducing factors
  • Cellular machinery which inhibit proliferation in response to metabolic imbalance and DNA damage
27
Q

What are the first 2 tumour suppressor genes that were extensively studied?

A
  • Rb
  • p53
28
Q

What kind of molecule is NF1? (2)

A
  • RasGAP
  • GTPase activating protein (GAP) which induces GTP hydrolysis by Ras, causing Ras inactivation
29
Q

What is caused by loss of function of NF1? (2)

A
  • Neurofibromatosis
  • Familial cancer syndrome which causes development of benign tumours in the PNS which can become malignant
30
Q

How does NF1 work normally? (2)

A
  • Normally, growth factors cause NF1 degradation and Ras signalling can proceed
  • Then NF1 levels increase to induce GTP hydrolysis by Ras and Ras inactivation
31
Q

What happens when NF1 is mutated? (2)

A
  • Causes non-functional NF1 so can’t inactivate Ras
  • Results in hyperactivation of Ras
32
Q

Why can’t Ras inhibitors be used in the case of NF1 null cells? (4)

A
  • Ras inhibitors only work for oncogenic forms of Ras
  • NF1 null cells contain normal Ras that is hyperactive due to lack of inhibition
  • Can’t inhibit normal Ras because it is needed in normal cells
  • Need to target downstream signalling of Ras
33
Q

How could you target NF1 null cells? (3)

A
  • AKT and mTOR pathway is downstream of Ras and is overactive in the absence of NF1
  • This is reversed by the inhibition of mTOR with rapamycin
  • Rapamycin treatment reduces proliferation in NF1 null cells
34
Q

What is APC?

A

Adenomatous Polyposis Coli gene

35
Q

What causes heritable colon cancer? (2)

A
  • Loss of function of APC gene causes the development of benign polyps which can become cancerous
  • Loss of APC is the first step in carcinogenesis followed by oncogenic mutations of Ras and mutations/loss of p53
36
Q

How does Wnt signalling regulate intestinal crypts? (4)

A
  • Stem cells are at the bottom of the intestinal crypts in close proximity to stromal cells which secrete wnt signalling
  • Wnt signalling stimulates proliferation of stem cells and progenitor cells in the bottom of the crypt
  • Proliferating cells migrate upwards to the top of the crypt, lose wnt signalling which causes differentiation
  • Differentiated cells undergo apoptosis and are shed within 3-4 days
37
Q

Why do intestinal cells migrate and shed? (2)

A
  • Intestinal cells in contact with the contents of the intestines can be easily damaged
  • Defensive mechanism to remove potentially mutated cells before they can give rise to cancer
38
Q

What kind of mutation causes colon cancer?

A

Mutations that block cell migration out of the crypt so they continue to proliferate and aren’t shed

39
Q

How does APC inactivation cause colon cancer? (4)

A
  • APC is not present at the bottom of the crypt, expression is increased further up
  • APC normally binds to β-catenin and mediates β-catenin degradation
  • APC inactivation causes β-catenin to accumulate in the cytosol and nuclear translocation
  • Results in excessive expression of growth-promoting genes causing colon cancer
40
Q

How does Wnt signalling cause intestinal cell proliferation? (3)

A
  • Wnt signalling at the bottom of the crypt increases β-catenin levels in the cytosol
  • β-catenin translocates into the nucleus and causes transcription of growth-promoting genes including myc
  • Causes cell proliferation and cells migrate out of the crypt
41
Q

What is seen in APC negative intestinal crypts? (2)

A
  • Crypts are enlarged (indicative of increased growth)
  • Increased nuclear β-catenin levels in the whole crypt rather than just at the bottom of the crypt
42
Q

What is the result of a loss of APC?

A

Increased nuclear β-catenin levels

43
Q

What is β-catenin?

A

Transcription factor

44
Q

What is VHL syndrome? (2)

A
  • Von Hippen-Lindau syndrome
  • Causes a hereditary predisposition to tumour development in the kidney, adrenal gland and blood vessels in the CNS and retina
45
Q

What causes VHL syndrome? (2)

A
  • Germ line mutations in the tumour suppressor gene VHL
  • VHL also inactivated in ~70% sporadic kidney carcinomas
46
Q

What does the VHL gene code for?

A

pVHL protein

47
Q

What is the function of normal pVHL? (2)

A
  • Normoxia: HIF-1α is hydroxylated by proline hydroxylase, pVHL binds to hydroxylated HIF-1α and causes ubiquitination and degradation of HIF-1α
  • Hypoxia: no activity of proline hydroxylase so no degradation of HIF-1α, HIF-1α accumulates and promotes transcription of target genes
48
Q

What are the target genes of HIF-1α during hypoxia? (3)

A

Genes involved in:
- Angiogenesis
- Erythropoiesis
- Glycolysis and glucose uptake

49
Q

What happens with pVHL in tumours? (3)

A
  • pVHL completely lost or mutations in the recognition site for hydroxylated HIF-1α
  • This means that HIF-1α is not degraded and is constitutively active in tumour cells regardless of oxygen levels
  • Causes excessive expression of growth promoting genes
50
Q

True or false: cells in culture can be transformed by RSV infection

A

True

51
Q

True or false: proto-oncogenes were the first oncogenes to be discovered

A

False (viral oncogenes)

52
Q

True or false: multiple genes are responsible for RSV-induced transformation

A

False

53
Q

True or false: H-ras is activated by a single nucleotide change

A

True

54
Q

True or false: the cancer phenotype is always dominant

A

False

55
Q

True or false: LOH is observed in the vicinity of a TSG

A

True

56
Q

True or false: APC is overexpressed in colorectal cancer

A

False

57
Q

True or false: VHL is inactivated in several cancers including kidney carcinoma

A

True

58
Q

What are the 2 main types of cancer-controlling genes?

A
  • Proto-oncogenes
  • Tumour suppressor genes
59
Q

What does NF1 regulate?

A

Negative regulator of Ras signalling

60
Q

What does APC regulate?

A

Negative regulator of β-catenin signalling

61
Q

What does pVHL regulate?

A

Negative regulator of HIF-1α transcription factors

L2 Stem Cells (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions