Tumour Pathology 4

Question 1

What is mitosis?

Answer 1

Mechanism of cellular replication

Question 2

What does mitotic division generate?

Answer 2

Two genetically identical daughter cells

Question 3

What is a cell cycle?

Answer 3

Time interval between miotic division

Question 4

What is the cell cycle made up of?

Answer 4

G0

G1

S

G2

M

Question 5

What happens during G0?

Answer 5

Left cell cycle and stopped dividing

Question 6

What happens during G1?

Answer 6

Synthesis of components needed for DNA synthesis

Question 7

What happens during S?

Answer 7

DNA synthesis

Question 8

What happens during G2?

Answer 8

Preparation for mitosis

Question 9

What happens during M?

Answer 9

Mitosis and cell division

Question 10

How much cell divisions occur per second in humans?

Answer 10

25 x 10⁶

Question 11

How many cells are in the body?

Answer 11

10¹³

Question 12

What does quality control insure?

Answer 12

Genetic fidelity:

Each cell must recieve a full chromosome compliment

Mutations in DNA sequences must not pass on

Question 13

What factors is the cell cycle control by?

Answer 13

External factors

Intrinsic factors

Question 14

What external factors control the cell cycle?

Answer 14

Hormones

Growth factors

Cytokines

Stroma

Question 15

What intrinsic factor controls the cell cycle?

Answer 15

Critical checkpoints (restriction point R)

Question 16

What does progress before and after restriction point R depend on?

Answer 16

Prior depends on external factors

After becomes autonomous

Question 17

Where is R?

Answer 17

At the end of G1

Question 18

What does G1 control mechanism ensure?

Answer 18

Everything is ready for DNA synthesis

Question 19

What does G2 control mechanism ensure?

Answer 19

Everything is ready for cell division

Question 20

What do checkpoints in G1 check?

Answer 20

Cell size is inadequete

Nutrition supply inadequete

Essential external stimulus lacking

DNA damage detected

Question 21

What do checkpoints in S check?

Answer 21

DNA is not replicated

Chromosome mis-alignment

Question 22

What do checkpoints in G2 do?

Answer 22

Cell size is inadequete

DNA damage is detected

Question 23

What are checkpoints?

Answer 23

Systems of cyclically active and inactive enzymes

Question 24

What is a catalytic subunit activated by?

Answer 24

Regulatory subunit

Question 25

What are cyclin dependant kinases (CDK)?

Answer 25

Catalytic subunits

Question 26

What are the catalytic subunits?

Answer 26

Cyclin-dependent kinases (CDK)

Question 27

What are cyclines?

Answer 27

Regulatory subunits

Question 28

What are the active enzyme component of checkpoints called?

Answer 28

CDK/cyclin complex

Question 29

What is the process of cyclines and cyclin dependant kinases?

Answer 29

1) Different CDKs and cyclines operate at sequential stages of the cycle 2) Active CDK/cyclin complex phosphorylates target proteins 3) Phosphorylation results in activation/inactivation 4) Substrates regulate events in the next cycle phase

Question 30

How are CDKs regulated?

Answer 30

CDKs are constitutively expressed in an inactive form, whereas cyclines accumulate and are destroyed as cycle progresses CDKs inhibitors (CKIs)

Question 31

What are the 2 families of CKIs?

Answer 31

INK4A family CIP/KIP family

Question 32

What do molecules of the INK4A family do?

Answer 32

Bind to CDK4 and 6 and prevent association of these with their cyclin regulatory proteins

Question 33

What are the members of the INK4A family?

Answer 33

P16^INK4A P15^INK4B P18^INK4C P19^INK4D

Question 34

What is a member of the CIP/KIP family?

Answer 34

P21^CIP1

Question 35

What do CDK inhibitors do?

Answer 35

Bind to the cyclin/CDK complexes

Question 36

What does the Retinoblastoma gene do?

Answer 36

Encodes a 110kDa phophoprotein (pRb) which is hypophosphorylated

Question 37

What does hypophosphorylated mean?

Answer 37

Phosphorylated to a less than normal extent

Question 38

What does phosphorylation do?

Answer 38

Increases a cells progress through the cycle

Question 39

What is pRb phosphorylated by?

Answer 39

Active cyclin D/CDK complex

Question 40

What does pRb target?

Answer 40

E2F transcription factor

Question 41

What does a hypphosphorylated/active Rb do?

Answer 41

Inactivates E2F

Question 42

What does a phosphorylated/inactive Rb do?

Answer 42

Loses affinity for E2F

Question 43

When is Rb active?

Answer 43

When it is hypophosphorylated

Question 44

When is Rb inactive?

Answer 44

When it is phosphorylated

Question 45

What does E2F do?

Answer 45

It is a potent stimulator of cell cycle entry. free E2F transcription factor activates vital target genes

Question 46

What does pRb binding to E2F do to the cell cycle?

Answer 46

Stops it

Question 47

What is carcinogenesis?

Answer 47

The initiation of cancer formation

Question 48

What is carcinogenesis caused by?

Answer 48

Mutation of genetic material that upsets the normal balance between proliferation and apoptosis

Question 49

What does uncontrolled proliferation lead to?

Answer 49

Tumours

Question 50

Loss of the ability to control proliferation is due to mutations in genes regulating?

Answer 50

Cell division Apoptosis DNA

Question 51

What is carcinogenesis caused by specifically?

Answer 51

Envrionmental agents Inherited

Question 52

What environmental agents can cause carcinogenesis?

Answer 52

Chemicals Radiation Oncogene viruses

Question 53

What is the process of chemical carcinogenesis?

Answer 53

1) Purine and pyrimidine bases in DNA are critically damaged by oxidising and alkylating agents 2) Chemical carcinogens or their active metabolites react with DNA forming covalent bound productes (DNA adducts) 3) Adduct formation at particular chromosome sites cause cancer

Question 54

What are critical targets for radiation damage?

Answer 54

Purines and pyrimidine bases in DNA

Question 55

What is the primary defect in cancer?

Answer 55

Uncontrolled proliferation due to cell cycle dysregulation

Question 56

What are 2 regulatory pathways that frequently cause cancer?

Answer 56

Cyclin D-pRb-E2F pathway P53 pathway

Question 57

What genes are the cause of dysregulation at G1 to S causing most cancers?

Answer 57

Rb CDK4 Cyclin D P16

Question 58

What is the function of P53?

Answer 58

Maintain genetic integrity

Question 59

How do P53 levels change in damaged cells?

Answer 59

They increase

Question 60

What does the increase of P53 in damaged cells do?

Answer 60

Induces a cycle arrest at G1 Facilitates DNA repair Severe damage of P53 leads to P53-induced apoptosis

Question 61

What happens if there is no P53 present?

Answer 61

No cell arrest Genetically damaged cells proliferate and form malignant tumours