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BMS 100 > Carcinogenesis > Flashcards

Carcinogenesis Flashcards

1
Q

found in all progeny, begins the process towards malignant transformation

A

Initiating mutation
- Essentially the first driver mutation
- Often include loss-of-function mutations in genes that maintain genomic integrity

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2
Q

mutation that increases
malignant potential of the cell

A

Driver mutation

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3
Q

mutation with low malignant
effect

A

Passenger mutation

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4
Q

Mutations that result in the attributes of malignant cells include:

A

excessive growth, local invasion, distant
metastasis

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5
Q

Gain-of-function mutations

A

increasing in function - functioning more than it typically would in a normal person
Proto-oncogenes

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6
Q

Generally loss-of-function mutations

A

Tumour suppressor genes

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7
Q

class of mutated genes that can be gain- or loss-of-function

A

Genes regulating apoptosis

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8
Q

what class of mutated genes are genes responsible for DNA repair?

A
  • Generally loss of function
  • Affected cells acquire mutations at an accelerated rate (aka genomic instability)
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9
Q

Once established, tumours evolve genetically based on ____________. This results in tumour cells being genetically ______________.

A

survival/selection of the fittest (only the best mutations win)

  • Resulting in tumour cells being genetically heterogeneous
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10
Q

Tumour subclones compete for access to _________ with the fittest subclones dominating tumour mass

A

nutrients

As a result, tumours become more aggressive over time

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11
Q

Tumours that recur after therapy are almost always found to be _________ to the initial treatment

A

resistant

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12
Q

what type of mutation class promotes excessive cell growth, even in the absence of normal growth-promoting signals

A

Mutation class - Oncogenes

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13
Q

how are oncogenes created?

A
  • created by mutations in proto-oncogenes (unmutated cellular counterparts)
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14
Q

genes that normally help cells grow and divide to make new cells, or to help cells stay alive.

A

Proto-oncogenes

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15
Q

growth factors or their receptors, signal transducers, transcription
factors, or cell cycle components

A

can be mutated and become an oncogene

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16
Q
  • Ras
  • PI3 K
  • Myc
  • Cyclins and cdks
    are all examples of?
A

proto-oncogenes

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17
Q

BRAF - point mutation, translocation - melanomas, leukemias, colon carcinoma and others

A

RAF

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18
Q

Transcriptional activators - translocation - Burkitt lymphoma

A

MYC

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19
Q

CCND1

A
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20
Q

CDK4

A
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21
Q

Downstream component of receptor tyrosine kinases signaling pathways

A

RAS

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22
Q

what is the single most
common abnormality of proto-oncogenes in human tumors

A

Point mutation of RAS family genes

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23
Q

RAS causes
____ of pancreatic adenocarcinomas and
cholangiocarcinomas

____ of colon, endometrial, and thyroid cancers

____ of lung adenocarcinomas and myeloid leukemias

A

90%
50%
30%

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24
Q

Important downstream signaler for lots of growth factors. What are some examples?

A

RAS
* EGF, PDGF, and CSF-1

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25
Q

Ras leads to the activation of what? This induces what type of transcription factors

A

Ras leads to the activation of MAP kinase which induces MYC
MYC induces cyclin, more cyclin = less checkpoints resulting it increased cell proliferation

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26
Q

What does PI3 induce?

A

AKT

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27
Q

what does AKT do?

A

AKT can promote cell cycle progression by activating cyclin A (CDK-1 for S phase) and cyclin D = increase in checkpoints

28
Q

what does AKT decrease/inactivate?

A

p21 and p27
these are important for inhibiting cyclins (inhibits apoptosis)

29
Q

Immediate early response gene. Induced by Ras/MAPK signaling

A

MYC (transcription factor)

30
Q

when increased, what does MYC do?

A

Increases cell proliferation & growth
Contributes of other hallmarks of cancer
- Warburg effect (eg. can upregulate glycolytic enzymes)
- increased telomerase activity (contributes to endless
replicative activity)
- May also allow more terminally differentiated cells to
gain characteristics of stem cells

31
Q

what is the Warburg effect

A

glycolytic enzymes are upregulated
- in this case, cancer cells choose pyruvate to lactic acid pathway for energy even though there is an abundance of oxygen

32
Q

increase _________ activity contributes to endless replicative activity

A

telomerase

33
Q

MYC is implicated in cancers of (3)

A

breast, colon, lung

34
Q

Which of the two cell cycle checkpoints regulated by CDK-cyclin complexes do you suppose is more important in cancer?

A

G1/S
- is the start transition
- if you can get it going and going rapidly, then it allows for more success
MORE mutations will be affiliated with the aspects that are checked at G1/S

35
Q

Products of _________________ apply brakes to cell proliferation. Therefore, abnormalities lead to..?

A

tumour suppressor genes
lead to failure of growth inhibition

36
Q

Rb, P53 and CKIs are examples of which mutation class gene?

A

Mutation class - Tumour suppressor
genes

37
Q

Activation of oncogenes isn’t enough for cancer induction, usually requires loss of _____________ genes as well

A

tumour suppressor

38
Q

in a normal cell, RB and p52 recognize genotoxic stress and respond by…

A

responds by shutting down proliferation

39
Q

RB

A
40
Q

CDKN2A

A
41
Q

TP53

A

the guardian of the genome

42
Q

Which tumour suppressor gene functions as a key negative regulator of the G1/S checkpoints

A

RB

43
Q

when is RB in its active form?

A

when it is hypophosphorylated

44
Q

what E2F induce?

A

transcription factors in the S phase

45
Q

what form is RB in to facilitate passing through the G1/S checkpoint?

A

hyperphosphorylated (inactive)

46
Q

what is gene considered the guardian of the genome and codes for p53 protein. This is also the most frequently mutated gene in human cancer

A
  • TP53
47
Q

what is the function of TP53?

A

Regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis

48
Q

what is P53 usually bound to?

A

Mdm2

49
Q

what does p53 induce synthesis of?

A

p21 - binds cell cycle progression
- p21 binds to CDKS (check-point proteins) to inactive that

this stops the cell cycle so that the DNA repair cell can be repaired

50
Q

P53 uses _____ and _____ for successful DNA repair

A

p21 and GADD45

51
Q

what will occur in a cell with mutations of loss of p53

A

there will be no cell cycle arrest, no DNA repair, no senescence
this will result in mutant cells and ultimately the expansion and additional mutations

52
Q

how does p53 arrest the cell cycle until DNA can be repaired?

A

p53 induces the synthesis of p21 which binds to and inhibits CDKs - to stop it from working as a result, this stops the cycle cell

53
Q

____ can also be silenced by hypermethylation rather than mutation. This is an example of a ________ change and occurs in some cervical cancers

A

p16 - by silenced by hypermethylation

54
Q

Inhibits Cdk4- Cyclin D complex (G1-CDK complex) needed for progression through the cell cycle - describes the function of what

A

p16

55
Q

What do you notice about the common oncogenes and tumour suppressor genes we have discussed?

A

G1/S
start transition

56
Q

At least 1 of the 4 key regulators of the cell cycle is dysregulated in the significant majority of all human cancers

A

p16, cyclin D, Cdk4, RB

57
Q

The wnt-B-catenin pathway normally promotes

A

cell-proliferation

58
Q

mutation in APC

A

excessive activity (gain of function of) of B-catenin

59
Q

All cancers display 8 fundamental changes in cell physiology:

A
  1. Self-sufficiency in growth signals
  2. Insensitivity to growth-inhibitory signals
  3. Altered cellular metabolism
  4. Evasion of apoptosis
  5. Limitless replicative potential
  6. Sustained angiogenesis
  7. Ability to invade and metastasize
  8. Ability to evade the host immune system
60
Q

Cancer cells take up high levels of glucose and
demonstrate increased conversion of glucose to lactate. Even in the presence of ample oxygen

A

Warburg effect

61
Q

Why do you suppose a cancer cell relies on glycolysis alone for ATP production?

A

it uses the byproduct of glycolysis as the building blocks for quick growth

Mitochondrial oxidative phosphorylation does not!

62
Q

cell permanently exits the cell cycle & never divides again

A

Senescent

63
Q

how can cancer cells evade senescence

A
  • Likely due to loss of functions mutations in p53 and p16
  • Allows cell to pass through G1/S checkpoint
64
Q

Cancer cells have also demonstrated the ability to express telomerase. what does this allow the cancer cell to do?

A

Remember telomerase is only very minimally expressed in most somatic cells

replicate indefinitely

65
Q
A

BMS 100 (37 decks)

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