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2.1 Cell and Molecular Biology > Carla - Proto-oncogenes > Flashcards

Carla - Proto-oncogenes Flashcards

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1
Q

What is the hypothetical series of events to form a cancer cell?

A
  1. Initial mutation inactivates a negative cell cycle regulator
  2. Next mutation overactivates a positive cell cycle regulator
  3. Third mutation inactivates a genome stability factor
  4. Additional mutations accumulate rapidly
  5. Cancer cell formed
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2
Q

What are proto-oncogenes?

A

Genes whose products promote cell growth and division

Positive cell cycle regulators

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3
Q

What do proto-oncogenes encode?

A

Transcription factors that stimulate expression of other genes

Signal transduction molecules that stimulate cell division

Cell-cycle regulators that move through the cell cycle

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4
Q

What is an oncogene?

A

A gene which can transform a cell into a tumour cell

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5
Q

What must happen to proto-oncogenes for them to become oncogenes?

A

They must gain an amplification or activating mutation that results in them gaining the ability to transform a cell into a cancer cell

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6
Q

What do oncogenes cause to happen to cells?
(4)

A

Hyperactive growth and division

Protection against apoptosis

Loss of respect for normal tissue boundaries

Ability to become established in diverse tissue environments

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7
Q

What causes the conversion of proto-oncogenes to oncogenes?

A

This happens through genetic alteration

It typically leaves a gene continuously switched on

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8
Q

Give five types of oncogenes

A

Ras

Myc

CDK4

BCR/ABL

BCL-2

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9
Q

What are the three RAS isoforms?

A

H-Ras
K-Ras
N-Ras

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10
Q

How does Ras acct as an oncogene?

A

The active or mutant versions are found in many cancers e.g. colorectal

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11
Q

What is Ras?

A

Gene that encodes p21

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12
Q

What are the two types of Myc?

A

c-Myc

N-Myc

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13
Q

How does Myc act an oncogene?
(3)

A

It is over expressed in colorectal and breast cancers

It is rearranged in lymphomas

It is amplified in breast cancers and neuroblastomas (n-Myc)

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14
Q

How does CDK4 act as an oncogene?

A

Its mutated in familial melanoma

It has sporadic mutations in other tumours

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15
Q

How does BCR/ABL act as an oncogene?

A

Chimeric gene produced from the fusion of genes through chromosomal rearrangements -> The Philadelphia Chromosome

Cause of most chronic myelogenous leukaemias

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16
Q

How does BCL-2 act as an oncogene?

A

It is overexpressed due to a t translocation in follicular lymphoma

17
Q

What type of mutation in Ras is commonly seen in cancer?

A

A single point mutation is seen

18
Q

What does the most common point mutation in Ras do?
(2)

A

The mutation results in the conversion of a Glycine to a Valine

This valine forms a protein that hydrolysis GTP to GDP very inefficiently

19
Q

How does Ras normally function?

A

It switches between active and inactive conformations

20
Q

What does a Ras mutation do to its activation?

A

It inhibits Ras GTPase activity thus locking it permanently in the active state

21
Q

What is Myc

A

A family of regulator genes and proto-oncogenes that code for transcription factors

22
Q

What does Myc do?

A

Responsible for:
-proliferation
-differentiation
-apoptosis
-metabolism

23
Q

What % of cancers are caused by Myc mutations?

A

40%

24
Q

What does c-Myc encode?

A

A transcription factor that forms a hetero-dimeric complex Max

25
Q

What is Max?

A

Myc-associated factor X

26
Q

What does the c-Myc/Max complex do?

A

Regulates the expression and activity of:
- cell cycle regulatory proteins
-Cyclins,
-CDKs,
-CDK inhibitors and
-E2F

27
Q

What is induction of c-Myc needed for?

A

It is necessary to drive quiescent cells into the S phase

28
Q

Cancer cells contain hundred of extra copies of proto-oncogenes, comment on these?
(3)

A

These extra copies exist as:

Extrachromosomal bodies (double minutes)

OR

Extensive tandem repeat insertions within the chromosome

29
Q

Comment on the over expression of Myc

A

Forms extrachromosomal bodies

Mutation arises from too many copies of the gene being present (mutation not in the gene itself)

30
Q

What is a chromosomal translocation?

A

A chromosomal rearrangement in which part of one chromosome is detached by double stranded DNA and subsequently joined to a second non-homologous chromosome

31
Q

What does chromosomal translocation result in?

A

Results in the tightly regulated promoter or regulatory elements for one gene being replaced by the regulatory DNA sequence elements a highly active promoter

32
Q

What causes mutations?
(8)

A

Chemicals
Radiation
Some viruses
Tobacco smoke
Red meat
Nitrites
Alcohol
Mould

2.1 Cell and Molecular Biology (26 decks)

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