Oncogenes And Tumour Suppressor Genes

Question 1

What are the major functional changes in cancer?

Answer 1

Increased growth
Failure to undergo apoptosis or senescence
Loss of differentiation
Failure to repair DNA damage

Question 2

How does increased growth happen in cancer?

Answer 2

Loss of regulation and stimulation of environment promoting growth

Question 3

What do oncogenes cause?

Answer 3

Gain of function- making cells divide

Question 4

What are oncogenes?

Answer 4

Altered gene whos product can act in a dominant fashion to help make a cell cancerous

Question 5

What is the normal version of oncogenes?

Answer 5

Protoconcogenes

Question 6

What do tumour supressor genes cause?

Answer 6

Loss of function- normal activity prevents cancer formation

Question 7

What is Rous’s protocol for inducing sarcoma in chickens?

Answer 7

Remove sarcoma and break up into small tissue chunks
Grind up with sand
Filter and collect filtrate through a fine-pore filter
Inject filtrate into young chickens
Observe sarcoma in injected chickens

Question 8

How is c-src captured by retrovirus?

Answer 8

The virus can acquire fragments of genes from the host at integration sites

Question 9

What is the c-src oncogene product?

Answer 9

60 kDa intracellular tyrosine kinase

Question 10

What can the C-Src oncogene do?

Answer 10

Phosphorylate cellular proteins and affect growth

Question 11

What are the ways to become an active oncogene?

Answer 11

Mutation/deletion
Gene duplication/amplification
Translocation

Question 12

What do gene duplications/amplifications do for oncogenes?

Answer 12

Increase synthesis of encoded proteins

Question 13

What are the four types of protein involved in the growth signal transduction pathway?

Answer 13

Growth factors
Growth factor receptors
Intracellular signal transducers
Nuclear transcription factors

Question 14

What do the majority of oncogene proteins function as?

Answer 14

Elements of the signalling pathways that regulate cell proliferation and surivival in response to growth factor stimulation

Question 15

What do the majority of oncogene proteins function as?

Answer 15

Growth factors, growth backer receptors and intracellular signalling molecules

Question 16

What were RAS oncogenes identified from?

Answer 16

Studies of two cancer causing cell lines

Question 17

What are RAS oncogenes?

Answer 17

Small GTPases that are normally bound to GDP in a neutral state

Question 18

What proportion of oncogenic activation of RAS is seen in human cancer?

Answer 18

30%

Question 19

What codons are the mutations in on RAS oncogenes?

Answer 19

12, 13 and 61

Question 20

What do the point mutations lead to in RAS oncogenes?

Answer 20

Loss of GTPase acting on the RAS protein that is normally used to inactivate the RAS GDP

Question 21

How do the RAS oncogene intracellular signal transducers work?

Answer 21

Binding of extracellular growth factor signal

• > Promotes recruitment of RAS proteins to the receptor complex
• > recruitment promotes RAS to exchange GDP for GTP (activates RAS)
• > activated RAS then initiates the remainder of the signalling cascade (mitogen activated protein kinases)
• > kinases ultimately phosphorylate targets such as transcription factor to promote expression of genes important for growth and survival

Question 22

What does the MYC oncogene family consist of?

Answer 22

C-MYC
MYCN
MYCL

Question 23

Where was the MYC oncogene family originally identified?

Answer 23

In avian myelocytomatosis virus

Question 24

What are MYC oncoproteins?

Answer 24

Transcription factors

Question 25

How much of the genome do the MYC oncogenes transcribe?

Answer 25

15%

Question 26

What are the major downstream effectors of MYC?

Answer 26

``` Those involved in: Ribosome biogenesis Protein translocation Cell cycle progression and metabolism Cell proliferation, differentiation, survival and immune surveillance ```

Question 27

What proportion of human cancers are affected by overexpression of MYC?

Answer 27

40%

Question 28

What does MYC encode?

Answer 28

Helix-loop-helix leucine zipper transcription factor

Question 29

How does MYC transactivate gene expression?

Answer 29

Dimerises with MAX (its partner protein)

Question 30

When is MYC activated (generally)?

Answer 30

Comes under the control of foreign transcriptional promotors

Question 31

What does activated MYC lead to?

Answer 31

Deregulation of the oncogene that drives proliferation as a result of chromosomal translocation

Question 32

What is burkitts lymphoma?

Answer 32

High grade lymphoma

Question 33

Who is affected by burkitts lymphoma?

Answer 33

Children aged 2-16

Question 34

Where do the chromosomal translocations occur in the MYC gene?

Answer 34

Parts of chromosomes 2, 14 and 22 attach themselves to chromosome 8

Question 35

Which accounts for 15-20% of leukaemia?

Answer 35

Chronic myelogenous leukaemia

Question 36

What proportion of chronic myelogenous leukaemia patients carry the philadelphia chromosome?

Answer 36

95%

Question 37

What is the result of the philadelphia chromosome generation?

Answer 37

Tyrosine kinase activity of the oncogene ABL leading to abnormal proliferation

Question 38

What are tumour supressor genes usually regulators of?

Answer 38

Cell cycle checkpoints, differentiation or DNA repair

Question 39

What does loss of tumour supressor gene function require?

Answer 39

Inactivation of both alleles of the gene

Question 40

Are tumour supressor genes dominant or recessive?

Answer 40

Recessive

Question 41

When do retinoblastomas occur?

Answer 41

When immature retinoblasts continue to grow very fast and do not turn into mature retinal cells

Question 42

How can you see retinoblastomas?

Answer 42

Tumour will reflect light back in a white colour

Question 43

What is leukocoria?

Answer 43

When the tumour reflects light back in a white colour

Question 44

What are the two forms of retinoblastoma?

Answer 44

Familial | Sporadic

Question 45

Where is the hereditary mutation in retinoblastoma?

Answer 45

chromosome 13

Question 46

What does the Rb gene family include?

Answer 46

Three members collectively known as pocket proteins

Question 47

How many binding partners does prb have?

Answer 47

Over 100

Question 48

What is the main function of the RB protein?

Answer 48

Regulate the cell cycle by inhibiting G1-S phase transition

Question 49

Which is the first cyclin to be synthesised?

Answer 49

Cyclin D

Question 50

What does Cyclin D do?

Answer 50

Drives progression through G1 with CDK 4/6

Question 51

What does the g1 checkpoint lead to if the DNA is damaged?

Answer 51

Arrest of the cell cycle

Question 52

What is a key substrate for cyclin D?

Answer 52

RB protein

Question 53

What is the main binding factor?

Answer 53

E2F transcription factor

Question 54

What is Rb activity regulated by?

Answer 54

Phosphorylation

Question 55

What happens when the Rb tumour suppressor is active?

Answer 55

Inhibits cell proliferation

Question 56

What happens when RB is dephosphorylated?

Answer 56

Active and remains bound to E2F

Question 57

What happens when RB is phosphorylated?

Answer 57

E2F is released and migrates to the nucleus to induce transcription

Question 58

What can RB be inactivated by?

Answer 58

Phosphorylation, mutation or viral oncoprotein binding

Question 59

How does viral inactivation in small DNA tumours mainly work?

Answer 59

Dirupting ELF binding or destabalisation of RB

Question 60

What was the first tumour supressor gene to be identified?

Answer 60

P53

Question 61

what is the prevelance of p53 mutation in cancers?

Answer 61

30-50%

Question 62

What does frequent mutation of p53 in tumour cell genomes suggest?

Answer 62

Tumour cells try to eliminate p53 function before they can thrive

Question 63

What are p53 levels kept low by?

Answer 63

MDM 2 protein

Question 64

What is the MDM2 protein made from?

Answer 64

Oncogene-ubiquitin ligase

Question 65

What happens in normal unstressed cells with MDM2 and p53?

Answer 65

Move between the nucleus and cytosol

Question 66

What happens with MDM2 and p53 in the nucleus?

Answer 66

Bind to form a complex where MDM modifies the carboxyl terminus of p53 and targets it for degredation by the proteasome

Question 67

What activates p53?

Answer 67

Stress signals