Cancer and the control of cell division

Question 1

Cancer is..

Answer 1

the disease of uncontrolled cell division. It usually comes about through mutations in a person’s DNA during their lifetime.

Question 2

Cancer is..

Answer 2

the disease of uncontrolled cell division

Question 3

Survival probabilities of cancer vary on:

Answer 3

the type of cancer and stage at diagnosis

Question 4

What are some low survival probability cancers?

Answer 4

Pancreatic
Lung
Oesophagus
Stomach

Question 5

What are some high survival probability cancers?

Answer 5

Melanoma
Testicular
Breast

Question 6

What are some risk factors for cancer?

Answer 6

Age
Environmental risk factors
Susceptibility genes

Question 7

What is the single biggest risk factor for cancer?

Answer 7

Age

Question 8

Why do we need to understand the cell cycle?

Answer 8

To understand abnormal cell division and understand pharmacology of chemotherapeutic agents that kill cells by disrupting the cell division

Question 9

What occurs in the cell division cycle?

Answer 9

Process in which a mother cell gives rise to two identical daughter cells.
This cycle is activated in adults to replace dead or damaged cells.

Question 10

The cell cycle has 4 discrete phases. Explain each stage

Answer 10

G1 - First gap phase. Cell growth.
S - DNA synthesis phase. All DNA in cell’s genome is replicated. Cell growth continues
G2 - Second gap phase. Cell growth. Checking for replication errors.
M - Mitosis phase, usually followed by cytokinesis. Chromosomes are partitioned into two daughter cells which finally divide

Question 11

MOST CELLS DON’T DIVIDE MOST OF THE TIME.

What are the three other types of cells?

Answer 11

• Some cells don’t divide at all
• Some differentiated cells retain the ability to proliferate.
• Some cells are replaced from stem cells.

Question 12

Some cells that cannot divide at all –> expand on when these are made and give an example

Answer 12

Some cell types are formed during embryonic development and are no longer capable of cell division. They cannot be replaced upon damage or cell death e.g. cardiac muscle or most neurones.

Question 13

Some differentiated cells retain the ability to proliferate –> expand on when these are made and give an example

Answer 13

These are normally in a resting state, called quiescence of G0 but are able to activate cell division to replace dead/ injured cells.
Example: smooth muscle cells, skin fibroblasts, endothelial cells that line blood vessels, and epithelial cells of organs like the liver.
Can show massive proliferation in response to damage e.g wounds or liver surgery

Question 14

What are stem cells?

Answer 14

They are not terminally differentiated themselves
They can divide without limit
When they divide, each daughter cell has a choice to either remain as a stem cell or to become terminally differentiated.
Stem cells are required whenever there is a recurring need to replace differentiated cell that cannot themselves divide.

Question 15

What are stem cells?

Give examples

Answer 15

They are not terminally differentiated themselves
They can divide without limit
When they divide, each daughter cell has a choice to either remain as a stem cell or to become terminally differentiated.
Stem cells are required whenever there is a recurring need to replace differentiated cell that cannot themselves divide.
Blood cells, epithelial cells of the skin and epithelial lining of the digestive tract.

Question 16

Entry into cell cycle is controlled by the availability of

Answer 16

growth factors

Question 17

The availability of growth factors controls the cell cycle at a point late in

Answer 17

G1 phase, called the restriction point.
If growth factors are not available during G1, the cells enter a quiescent stage of the cycle known as G0.
Cells have a limited proliferation capacity and will eventually enter G0 permanently (replicative senescence)

Question 18

What a growth factors?
What are they also referred to as? Give examples.
They are triggers of

Answer 18

Signalling molecules that stimulate cell division.
Mitogens. PDGF, FGF, EGF
They are triggers of complex cell signalling cascades

Question 19

Cell signalling is a pathway which relays information from the cell s______ to the int_____, where it can either ______ protein behaviour or cause ______ synthesis

Answer 19

surface
interior
alter
protein

Question 20

Direct cell signalling occurs via

Answer 20

protein phosphorylation

Question 21

Indirect cell signalling occurs via

Answer 21

GTP-binding protein

Question 22

What is the most commonly used molecular switch?

Answer 22

Phosphorylation

Question 23

What receptor do most growth factors act on?

Answer 23

Tyrosine Kinases

Question 24

What is the mechanism of signalling molecules after they bind on tyrosine kinase receptor?

Answer 24

RTKs dimerise to activate kinase domain, which in turn phosphorylates a range of further intracellular signalling proteins.

Question 25

Most RTKs activate ____, a small ____-binding protein, which is mutated in many human _____

Answer 25

Ras
GTP
CANCERS

Question 26

Ras feeds into many different intracellular signalling pathways. One of these, the

Answer 26

Mitogen activated kinase pathway acts as phosphorylation cascade.
Phosphorylation eventually alters protein activity and causes changes in gene expression.

Question 27

One of the most important proteins synthesised in response to growth factor signalling are

Answer 27

D-type cyclins. Cyclins are proteins that undergo synthesis and degradation in timing with different phases of the cell cycle. Cyclin levels are high during mitosis and low during interphase

Question 28

Cyclin levels are high during _____ and low during _______

Answer 28

mitosis

interphase

Question 29

Cyclins are small proteins that are essential for the activity of

Answer 29

cyclin-dependent kinases (Cdks)

Question 30

Cyclins are small proteins that are essential for the activity of

Answer 30

cyclin-dependent kinases (Cdks).

Question 31

Cyclins activate Cdks and together they initiate the

Answer 31

events of the cell cycle i.e DNA replication, mitosis

Question 32

Compare the levels of Cdks and cyclin.

Answer 32

Cdk levels remain relatively constant during cell cycle, but cyclin levels change.

Question 33

Cdks themselves are further regulated by:

and can be inhibited by:

Answer 33

phosphorylation

Cdk-inhibitor proteins (CKIs)

Question 34

The availability of cyclins controls the activity of ____ and promotes _____ progression

Answer 34

cdks

cycle

Question 35

For the following CYCLIN-CDK complexes, give the cyclin and CDK partner involved in VERTEBRATES

• G1
• G1/S
• S
• M

Answer 35

• cyclin D and CDK 4, CDK6
• cyclin E and CDK 2
• cyclin A and CDK 2, CDK 1
• cyclin B and CDK 1

Question 36

The CDK partner for all budding yeasts is _____. This was previously known as

Answer 36

CDK1

cdc28

Question 37

Explain how MapKinase signalling and CDKs work together/ are relayed?

Answer 37

Mitogen signalling is relayed from the cell surface via a signalling cascade through to the synthesis and action of CDK/ cyclin complexes.

Question 38

What are the three steps involved in MAPkinase signalling?

Answer 38

1. Receptor/ mitogen interaction leads to transcription of new proteins via MAP kinase phosphorylation
2. These early regulatory proteins trigger the transcription of cyclin D
3. Main target of cdk4 and 6/cyclin D is RB protein.

Question 39

What is the main target of cdk4 and 6/ cyclin complex? What happens once it is phosphorylated?

Answer 39

Rb (retinoblastoma protein)
Once Rb is activated, it frees E2F protein, to act as a transcription factor on many S-phase genes, leading to cell entry.

Question 40

An animal cell depends on multiple extracellular signals. Give examples

Answer 40

Cytokines
Growth factors
Death factors
Hormones

Question 41

To ensure control of cell cycle exit, there are several _________. Which function to ensure that ……

Answer 41

checkpoints

complete genomes are transmitted to daughter cell.

Question 42

One major checkpoint arressts cells in ____ phase in response to damage or unreplicated DNA

Answer 42

G2

Question 43

checkpoint in M phase, arrests mitosis if

Answer 43

daughter chromosomes are not properly aligned on the mitotic spindle.

Question 44

presence of damaged DNA also leads to cell cycle arrest at a checkpoint in

Answer 44

G1

Question 45

The G1 checkpoint is mediated by a transcription factor called

Answer 45

P53

Question 46

Increased DNA damage levels leads to ______ levels of p53

Answer 46

increased

Question 47

50% of cancers have a mutation in ___ transcription factor

Answer 47

p53

Question 48

p53 also causes the transcription of ___, a cdk inhibitor.

cdk inhibition prevents cell cycle ________

Answer 48

p 21

progression

Question 49

p 21, a cdk inhibitor, also acts as a _ _ _ _ inhibitor, inhibiting DNA replication

Answer 49

PCNA

Question 50

P53 stops cell division to allow for ____ repair

Answer 50

DNA

Question 51

P53 stops cell division to allow for ____ repair. However, where the damage is irreparable, p53 initiates signalling pathways that lead to programmed cell death or _______

Answer 51

DNA

apoptosis

Question 52

Chemotherapeutic agents stop cancer cell division by blocking DNA replication (which occurs at ___ stage), and some by blocking mitosis (which occurs at __ stage).

Answer 52

S

M