Oncogenes 2

Question 1

STAT

Answer 1

survival, proliferation and oncogenesis

Question 2

Akt

Answer 2

angiogenesis, tumorigenesis and inhibition of apoptosis

Question 3

ERK

Answer 3

gene expression and cell-cycle progression

Question 4

PKC

Answer 4

transformation, differentiation and apoptosis

Question 5

What is unique about HER receptors?

Answer 5

Some don’t show any ligand - activated on nearby receptor activation

Question 6

DNA rearrangement mutations in HGF-R and c-Met HGF-R heterodimer

Answer 6

localized on cellular membranes.
The unmutated receptor makes cell motile for them to be able to move. It has two ligand binding domains bound by disulfide bonds. The mutated receptor has a translocation, the c-Met fragment of the cytoplasmic domain is fused to another cytosolic protein, and ligand binding is not able to regulate the receptor activity anymore.

Question 7

Result of HGF-R and c-Met HGFR mutation

Answer 7

This re-arrangement results in aberrant localisation and activation of Met tyrosine kinase activity, and it was identified in sarcomas.

Question 8

HGF-mediated signaling

Answer 8

• > regulates diverse cellular processes
• Prosurvival signaling and motility are regulated, as well as proliferation.
• Chromosomal translocation 9-22 produces an oncogene that constantly signals downstream without the need for a receptor or a ligand, nevertheless.

Question 9

Small GTPases are _______ in cancer, and they are really important in _______ due to their role in ____________

Answer 9

deregulated
cell structure
actin cable formation inside the cell.

Question 10

E-cadherin

Answer 10

keeps cell together in normal cells.

Question 11

Mutations in small GTPases

Answer 11

weaken the cell-cell junctions and allow metastasis by decreasing E-cadherin expression. Polarity is messed up so cells grow on top of each other in 3D .

Question 12

Matrix metalloproteases

Answer 12

provide cells enough motility to move around the body and they have a distinct role in metastatic growth.
-> digest the basal membrane and connective tissue, allowing them more freedom of movement and proliferation.

Question 13

5 main effects of Matrix metalloproteases

Answer 13

1. Release of growth factors
2. Degradation of matrix barriers
3. Degradation to reveal cryptic sites (laminin 5 and angiotensin)
4. Disruption of cell-matrix adhesion
5. Disruption of cell-cell adhesion

Question 14

Which MMP’s are overexpressed in malignant growth

Answer 14

2 and 9

Question 15

The most important domain in MMP’s are

Answer 15

the furin cleavage site, which acts as the autoinhibitory region for the enzyme’s catalytic activity.

Question 16

Why is the furin cleavage site important?

Answer 16

1. It folds and binds to the catalytic domain, it would only be activated when there is another protease called furin.
2. If there is no furin, the protein would remain inactive.
   Combination of events is necessary for activity.

Question 17

Angiogenesis

Answer 17

new blood vessels form from preexisting blood vessels

Question 18

VEGF expression leads to

Answer 18

Neovascularization of the tumor

Question 19

What are 2 mechanisms by which cancer cells maintain a lower rate of apoptosis?

Answer 19

1. Bcl-2 is a proto-oncogene, which inhibits the protease cascade that leads to cell death.
2. PI3K / Akt signalling regulates cell survival pathway
   - Overexpression or activating mutations in Bcl2, PI3K, and PKB / Akt are found in many types of human cancer.

Question 20

What is used instead of pyruvate in glycolysis of cancer cells?

Answer 20

Pyruvate Kinase M2

Question 21

mTOR stands for

Answer 21

mammalian target of tropomyosin

• serine/threonine kinase that lacks the substrate binding sequence
• key regulator for anabolic and catabolic biological events uses small GTPases to sense amount of ATP and monomers present and the level of growth factor signalling.

Question 22

How do AMP kinase phosphorylate tumor suppressors?

Answer 22

G1/S checkpoint is controlled by phosphorylation of Rb by cyclin-dependent kinases, and deregulation of this checkpoint (cyclin D1 overexpression or inactivation of CDK inhibitors) would contribute to malignant growth.

Question 23

Properties of Transformed Cells

Answer 23

1. Reduced requirement for growth supplements (serum, growth factors, hormones).
2. Loss of capacity to go into quiescent arrest (growth arrest)
3. Altered morphology (look different from precursors)
4. Loss of contact inhibition (tumor cells grow on top of each other)
5. Loss of anchorage dependence (tumor cells grow in soft agar)
6. Form tumor in “nude” mice.
   - > Many cancer cell lines, derived from naturally occurring tumors have these properties in culture.