Lectures 3 + 4 - Growth Factors and Cell Cycle Control

Question 1

What are growth factors?

Answer 1

Polypeptide signalling molecules which bind to cells to regulate growth, either stimulatory or inhibitory

Question 2

Give 4 examples of growth factors

Answer 2

Platelet-derived growth factor
Fibroblast growth factors
Epidermal growth factor
Transforming growth factor B

Question 3

What is special about transforming growth factor B?

Answer 3

Acts as a growth inhibitor in epithelial cells
BUT
Growth stimulator in fibroblasts

Question 4

What are the 2 types of GF receptors?

Give an example of a GF which binds to each

Answer 4

Serine/threonine kinase receptors - transforming GF B

Tyrosine kinase receptors - EGF

Question 5

Can you give an example of how growth factor receptors are important in cancer?

Answer 5

Overexpression of the epidermal growth factor receptor “Her2” can lead to breast cancer

Question 6

Can you name another receptor which is involved in breast cancer?
Name a drug to block this, and one to block Her2

Answer 6

Oestrogen receptor - Tamoxifen

Her2 - Herceptin

Question 7

What changes do you get in cancer which drive proliferation (4) ?

Answer 7

• Autocrine stimulation
• Receptor amplification
• Paracrine stimulation
• Mutation leading to proliferation in absence of ligand

Question 8

List the stages of the cell cycle, and what occurs during each stage

Answer 8

• G1 - cellular contents duplicated
• S - DNA replication
• G2 - double-check for errors
• Mitosis - prophase, metaphase, anaphase, telophase
• Cytokinesis - physical separation of the 2 cells

Question 9

What are cyclin-dependent kinases?

Answer 9

Serine-threonine kinases which are only active when bound to cyclins
Vital in cell cycle control

Question 10

Name an example of a CDK inhibitor

Answer 10

p16

Question 11

What controls the G1-S transition phase?

Answer 11

Retinoblastoma protein, along with CDKIs

Question 12

Briefly outline the normal Wnt/B-catenin pathway

Answer 12

• B-catenin activates the transcription of certain genes
• Only occurs when it builds up in cytoplasm and is then translocated into the nucleus where it activates transcription
• When transcription is not appropriate, B-catenin is broken down in cytoplasm so it doesn’t accumulate. APC important in this process
• When transcription needed, Wnt pathway activated - prevents destruction of B-catenin - accumulates

Question 13

How is the Wnt/B-catenin pathway implicated in colon cancer?

Answer 13

Mutated APC means B-catenin not broken down - inappropriate transcription of genes driving cell proliferation
May also be mutation to B-catenin itself meaning it evades breakdown

Question 14

How does the Wnt/B-catenin pathway link to G1-S transition regulation?

Answer 14

B-catenin drives transcription of cyclin D1 (amongst others) - drives cell progression by activating CDKs

Question 15

What controls G2 - M transition?

Answer 15

CDK1-cyclin B complexes

Question 16

What happens at the G2-M checkpoint if DNA is damaged?

Answer 16

2 serine/threonine kinases activated
In turn activate WEE1 which phosphorylates the CDK-cyclin complex –> inactive
Also activated p53 which activates p21, a CDKI

Question 17

What happens at the G2-M checkpoint if the DNA is intact?

Answer 17

CDK1-cyclin B complex activates mitosis promoting factors - triggers mitosis