Oncogenes

Question 1

What are the hallmarks of cancer?

Answer 1

independence in growth signals
don't respond to anti-apoptotic signals
limitless replication
sustained angiogenesis
altered metabolism
evasion of immune system
inflammation
genomic instability
ability to evade and metastasis

Question 2

How do proto-oncogenes turn to oncogenes?

Answer 2

Through point mutations, translocations, deletion, gene amplification

Question 3

What are the types of point mutations?

Answer 3

missense
nonsense
frameshift

Question 4

How can translocation change gene function and regulation?

Answer 4

It can be translocated near an overactive promoter resulting in overexpression of the gene

Question 5

What are the configuration gene amplification causes?

Answer 5

1. Double minute-tiny extrachromosomal bodies that segrate randomly during mitosis
2. Homogeneously staining regions-expanded regions on the chromosomes without normal banding patterns

Question 6

How does gene amplification contribute to oncogenesis?

Answer 6

By transcribing a large amount of MRNA

Question 7

If deletions occur in multiples of 3’s then no frameshift will occur

Answer 7

True

Question 8

What proteins can be oncogenes?

Answer 8

Trnascription factors, tyrosine kinase receptors or proteins, growth factors, secondary molecules

Question 9

What are some examples of growth factors that can act as oncogenes?

Answer 9

FGF, PDGF, TGF-A(breast cancer viaEFGR)

Question 10

How is the growth receptor activated?

Answer 10

Ligand binds receptors dimerize, conformational change and it oligomerizes, the intracellular domain is transphosphorylated by kinase activity and recruits secondary molecules and this initiates a signalling cascade

Question 11

How can receptor growth factor contribute to cancer? Give exmaples

Answer 11

They can be overexpressed suh as c-erb(valine to glutamine causes neuroblastoma)
Or can be mutated such as v-erb both lead to constitutive activation

Question 12

Steroid receptor, outline main steps. Give example of a mutation that occurs in steroid receptor and causes cancer

Answer 12

They are bound to a receptor and heat shock proteins when a ligand binds it will dissociate from the hsp complex and tranlocates to the nucleas binds to HRE and transcribes genes.
ABL;PAR translocation form a fusion protein one binds to DNA the other has transactivating function- Leukaemia

Question 13

How are protein kinases mutated, give examples

Answer 13

Src-mutated then can lose cell cell adhesion-metastasis and can deregulate cell cycle
, c-abl- translocation of of abl from chromosome 9 to chromosome22, abl is constitutively expressed because of the strong promoter it is next to, found in CML

Question 14

What is src what is important for?

Answer 14

SRCis a kinase that phosphorylates intracellular domian of kinase receptor, it’s on the plasma membrane. Important for cell-cell adhesion and cell cycle regulation via sam68

Question 15

What drug can be used to treat bcr-abl philadiphea chromosome? And what are some problems with it?

Answer 15

sti-571 inhibitor against the signalling of bcr-abl

It is non specific, mutation arise and express AGP making it resistant to the drug later on.

Question 16

What is myc and how does it work? What regulates it?

Answer 16

myc is a transcription factor that binds to max and translocates to nucleas to bind to e-box element on DNA
Important in regulating the cell cycle, apoptosis,metabolism, cell adhesion, differentiation. It inhibits p27 and activates cyclin-cdk complexes
Other myc families, APC regulates it through the wnt pathway

Question 17

WHat is c-jun and how does it work?

Answer 17

Fos binds to jun after it gets proliferative and differentiation signalling, then it binds to AP1 sites

Question 18

What is ras? How is the MAPK activated?

Answer 18

a 21kda guanine nucleotid ebinding protein(p21ras)
Ligand binds, ras is phosphorylated by GAP(P120), it oactivates raf, which activates MAPKKK, which activates MAPKK and then MAPK which goes to the nucleus and trasncribe genes. Gtpase turns ras off and the signalling cascade is all turned off.

Question 19

Which codons have ras muations? What are the different RAS genes?

Answer 19

12,13,61

N,H,K

Question 20

What is NF1

Answer 20

It is a tumour suppresson gene, homologous to ras

Question 21

What are ways to target ras?

Answer 21

antisense oligos or RNA
farensyl transferase inhibitor
RNAi