Cancer 2

Question 1

Cells need to be attached to ECM and they need a certain degree of spreading to be able to respond to soluble growth factors. What is the term given to the requirement of ECM binding for growth?

Answer 1

Anchorage dependence

Question 2

integrins structure

Answer 2

heterodimers consisting of alpha and beta subunits

main role is to allow cell to interact with ECM

Question 3

what do integrins bind to on the cytoplasmic side

Answer 3

actin

exception- a6b4 integrin complex found in epithelial hemidesmosomes, are linked to the cytokeratin in the cytoplasm

Question 4

2 types of cell cell junctions

Answer 4

Zonulae (belts)

Maculae (spots)

Question 5

What effect does low calcium levels have on an epithelium?

Answer 5

Many cell-cell junctions are calcium dependent
In the absence of calcium/low calcium, the junctions will break down, leading to:
- Increased MAPK activation (pro-proliferation)
- Decrease activity of p27KIP1 (its a Cdk inhibitor)
- INCREASED PROLIFERATION
When calcium returned to normal and the junctions are reformed:
- Decreased MAPK activation
- Increased activity of p27KIP1 (Cdk inhibitor)
- DECREASED PROLIFERATION

Question 6

what is contact inhibition of proliferation

Answer 6

When bound to cadherin at the plasma membrane, beta-catenin is NOT available to bind to LEF-1 and cause nuclear effects
Cytoplasmic levels of beta-catenin can rise if there is:
- Inhibition of degradation of b catenin
- Loss of cadherin-mediated adhesion
This can lead to the formation of beta-catenin/LEF-1 complexes that promote proliferation

Question 7

What 2 types of dependences are needed for cells to proliferate

Answer 7

anchorage dependence (ECM interaction with cell promotes proliferation)
density dependence (density of cells affects how much growth factors can interact with cells. growth factors will then lead to proliferation) 
slide 51

Question 8

What are the counter-part oncogenes of the proto-oncogenes c-Raf and c-Jun?

Answer 8

v-raf and v-jun

Question 9

Types of cytotoxic chemotherapies

Answer 9

Alkylating agents 
Pseudoalkylating agents 
Antimetabolites 
Anthracyclines 
Vinca alkaloids and taxanes 
Topoisomerase inhibitors

Question 10

give 3 receptors overexpressed in cancers

Answer 10

PDGFR (platelet derived growth factor) (glioma/brain cancer)
EGFR (breast + colorectal)
HER2 (breast)

Question 11

Give 2 examples of constitutive activation of tyrosine kinase receptors in cancers

Answer 11

EGFR – lung cancer

FGFR – head and neck cancers, myeloma

Question 12

Give an example of of overexpression of ligand in cancer

Answer 12

VEGF (the ligand) – prostate cancer, kidney cancer, breast cancer

Question 13

which caspases are effector caspases

Answer 13

3, 6 and 7

Question 14

which caspases are initiator caspases?

Answer 14

2 8 9 10

Question 15

name an alkylating agent (a subtype of cytotoxcic chemotherapies)

Answer 15

chlorambucil

Question 16

Define necrosis

Answer 16

Unregulated cell death associated with trauma, cellular disruption and an INFLAMMATORY response

Question 17

define apoptosis

Answer 17

controlled cell death, with controlled cell disassembly, no inflammation

Question 18

Caspase stands for what

Answer 18

Cysteine-dependent aspartate-directed proteases