Cell Death And Cancer

Question 1

What is the role of p53 ?

Answer 1

The p53 protein is the guardian of the genome and it plays a central role in the checkpoint pathways of the cell cycle

Question 2

Summarise DNA damage

Answer 2

• DNA damage arises as a result of normal cellular processes
• single and double stranded breaks in DNA trigger activation of the ATM protein kinase enzyme
• double stranded breaks are caused by environmental exposure
• single stranded breaks in DNA are the most common with ~ 10000 per day as a result of spontaneous DNA decay

Question 3

What is the response to double stranded DNA breaks ?

Answer 3

• ATM phosphorylates checkpoint kinases which phosphorylate p53
• phosphorylated p53 is unable to bind Mdm2
• phosphorylated p53 is protected from degradation and this activates 2 events : cell cycle arrest and cell death
• phosphorylated p53 activates the gene coding for p21 that halts progression of the cell cycle by inhibiting activity of different Cdk-cyclins

Question 4

What is the key protein in the cell death pathway ?

Answer 4

Puma (p53 upregulated modulator of apoptosis) is the key protein which inhibits Bcl-2 (an apoptosis inhibitor) and so cell death can occur

Question 5

What is the role of Ras proteins ?

Answer 5

• the Ras pathway synthesises cyclins and Cdks
• Ras proteins play an essential role in transduction of signals from cell surface receptors to the nucleus

Question 6

Summarise the Pl 3-Kinase-Akt pathway

Answer 6

• activated by stimulatory growth factors
• leads to cell death (apoptosis) or cell survival and proliferation (growth)
• ultimately leads to Akt phosphorylation

Question 7

Which 2 pathways does Akt mediate ?

Answer 7

• cell death (apoptosis)
• cell growth

Question 8

How are damaged and diseased cells eliminated ?

Answer 8

By apoptosis and necrosis

Question 9

What is apoptosis ?

Answer 9

• programmed cell death in which singular cells are killed
• involves dismantling the nucleus and the cell contents with no inflammation

Question 10

What is necrosis ?

Answer 10

• a type of cell death involving more than 100 cells
• it involves swelling and rupture of injured swells

Question 11

Describe the steps of apoptosis

Answer 11

1) as cell begins apoptosis the cell shrinks and the chromatin condenses
2) fragmentation of the nucleus occurs and individual parts of the cell are fragmented so there is no inflammation
3) apoptic bodies form so they can be engulfed by phagocytosis

Question 12

What is the role of caspases ?

Answer 12

Caspases are the proteins that control apoptosis

Question 13

What are the 2 main routes of apoptosis ?

Answer 13

• intrinsic route
• extrinsic route

Question 14

Describe the extrinsic route of apoptosis

Answer 14

1) a death receptor is embedded in the host cell and a cytotoxic T lymphocyte binds to it
2) the initiator procaspase matures into an initiator caspase and the executioner procaspase matures into an executioner caspase
3) apoptosis is activated

Question 15

Give an example of a pro apoptotic protein

Answer 15

Bad : Bcl-2-associated death promoter

Question 16

Describe the intrinsic route of apoptosis

Answer 16

1) initiated by signals from within the cell
2) regulated by maintaining a balance between 2 proteins found in the mitochondrial membrane
3) mitochondrial substances such as cytochrome c and calcium leak out into the cytoplasm
4) caspase-9 is assembled into a complex known as an apoptosome

Question 17

What is cancer ?

Answer 17

A disease that arises from abnormalities of cell function
- there are ~ 200 types in humans

Question 18

What percentage of all cancers are derived from a mutation of p53 ?

Answer 18

75%

Question 19

What is cell differentiation ?

Answer 19

A process of cells acquiring specialised properties

Question 20

Summarise the differences between normal growth of cells and tumour growth

Answer 20

• in normal growth each cell division gives rise to 1 cell which has the capacity to divide and 1 cell which has the capacity to differentiate and so there is no net accumulation of dividing cells
• in tumour growth each cell division is not balanced with death or differentiation and so there is a net increase in the number of cells dividing

Question 21

What are the 2 types of tumours ?

Answer 21

1) benign - grow in a confined local area and are rarely dangerous
2) malignant - invade surrounding tissues and spread to parts of the body

Question 22

Give some characteristics of benign tumours

Answer 22

• cells tend not to spread
• most grow slowly
• do not invade nearby tissue
• do not metastasise

Question 23

Give some characteristics of malignant tumours

Answer 23

• cells can spread
• usually grow fairly rapidly
• often invade nearby tissues
• may recur after removal

Question 24

How are cancer cells immortalised ?

Answer 24

Most cancer cells produce telomerase - an enzyme that adds telomere sequences to the ends of DNA molecules causing immortality of cancer cells

Question 25

What is the multi step process through which cancer arises ?

Answer 25

1) initiation - normal cells are converted into a pre cancerous state and sensitised to further change
2) promotion - sensitised cells are repeatedly exposed to cancer promoting agents
3) tumour progression - once a tumour is formed it will grow and differentiate

Question 26

What is angiogenesis ?

Answer 26

It is the development of new blood vessels
- required for tumours to grow beyond a few millimetres in diameter

Question 27

What is invasion ?

Answer 27

Direct migration and penetration of cancer cells into neighbouring tissues

Question 28

What is metastasis ?

Answer 28

The ability of cancer cells to enter the bloodstream and travel to distant sites

Question 29

Describe the process of metastasis

Answer 29

1) cancer cells invade surrounding tissues and vessels
2) cells are transported by the circulation system
3) cells re invade and grow at new locations

Question 30

Give 6 hallmarks of cancer

Answer 30

1) self sufficiency in growth signals
2) insensitivity to antigrowth signals
3) evasion of apoptosis
4) limitless replication potential
5) sustained angiogenesis
6) tissue invasion and metastasis

Question 31

Describe the process of necrosis

Answer 31

1) reversible swelling of the cell
2) eventually will get irreversible swelling of the cell
3) disintegration of the cell