Session 2 - Growth Factors and Receptors

Question 1

Give two main forms of extra-cellular signalling molecules

Answer 1

1. Polypeptides (growth factors)
   a. act through receptors on the cell membrane
   e. g. hormones and cytokines
2. Low molecular weight molecules
   a. these traverse the cell membrane and bind to intracellular receptors

Question 2

Give three methods of extracellular signalling

Answer 2

Endocrine
Paracrine
Autocrine

Question 3

What is endocrine?

Answer 3

hormones transported by the blood stream

Question 4

Paracrine?

Answer 4

Molecule produced locally by one cell and has effect on another cell

Question 5

Autocrine

Answer 5

Molecule produced locally and has same effect on same cell

Question 6

What are growth factors?

Answer 6

Growth factors are ligands which bind to growth factors receptors on cell membranes, inducing intracellular signal transducers and subsequently transcription factors in order to have an effect on the growth and development of a cell.

Question 7

Give three roles of growth factors

Answer 7

• Regulation of growth (can inhibit as well as stimulate)
• Inducing maturation and maintain differentiation in normal tissues
• Have an important role in healing and repair

Question 8

Give five types of growth factor

Answer 8

Platelet Derived Growth Factor
Fibroblast Growth Factors
Epidermal Growth Factor 
Transforming Growth Factor A
Transforming Growth Factor B

Question 9

What produces platelet derived growth factor?

Answer 9

Platelets and other, non-platelets

Question 10

What does PDGF do?

Answer 10

. Stimulates proliferation of stromal cells and endothelial cells by paracrine mechanisms and is therefore important in angiogenesis.

Question 11

What do fibroblast growth factors do?

Answer 11

Stimulate proliferation of fibroblast, endothelial cells and smooth muscle cells. Also angiogenic.

Question 12

Give two examples of cancers in which Epidermal Growth Factor Receptor is targeted

Answer 12

Breast and lung cancer

Question 13

What does transforming growth factor A do normally?

Answer 13

Induces epithelial development.

Question 14

What does TGF A do in breast cancer?

Answer 14

Mediates mitogenic effects of oestrogen and is responsible for autocrine growth stimulation

Question 15

What five jobs does Transforming Growth Factor B do?

Answer 15

acts as a growth inhibitor in epithelial cells, but a growth stimulator in fibroblasts. Stimulates production of extracellular matrix by increasing synthesis and decreasing degradation. Also mediates immune system by blocking activation of lymphocytes/macrophages and can stimulate angiogenesis.

Question 16

What role does TGF B have in cancer?

Answer 16

By promoting angiogenesis and blocking and immune response to the cancer.

Question 17

Give two types of growth factor receptor?

Answer 17

• Serine/Threonine Kinases

- Tyrosine Kinase Receptors

Question 18

Give an example of Serien/Threonine Kinases?

Answer 18

A receptor found in many cancers, examples include both types (1 and 2) of the receptor for Transforming Growth Factor B.

Question 19

Give three examples of tyrosine kinase receptors

Answer 19

• Type 1 – Epidermal Growth Factor Receptor
• Insulin Growth Factor Receptor
• PDGF receptor

Question 20

What cancers are Epidermal Growth Factor Receptors involved in?

Answer 20

Squamous Carcinomas and activating mutations in lung cancer

Question 21

Where are HER-2 receptors found, and in what cancer aeitologies does it cause problems?

Answer 21

gene amplification and over-expression is found in adenocarcinomas and 20% of breast cancer

Question 22

How do you treat HER-2 positive breast cancer?

Answer 22

Herceptin

Question 23

Give two examples of steroid hormones

Answer 23

Androgens

Oestrogens

Question 24

What cancers are androgens involved in?

Answer 24

gene amplification and over-expression is found in adenocarcinomas and 20% of breast cancer

Question 25

Give two cancers oestrogen is involved in?

Answer 25

Breast and endometrial cancer

Question 26

What does retinoic acid do?

Answer 26

Induces differentiation in cancer cells of Acute Myeloid Leukaemia, therefore slowing disease progression

Question 27

What are the three main domains of steroid receptors?

Answer 27

• Hormone binding
• DNA binding
• Transactivating (induce transcription)

Question 28

Give the sequence of events of steroids interacting with receptors?

Answer 28

Steroids interact with receptor -> Specific binding to hormone response element in DNA -> Transcription factors and RNA polymerase recuited to iniate transcription of target genes _> Protein synthesised -> Functional response

Question 29

How do cancer cells interact with growth factors differently to normal cells?

Answer 29

They have a lower requirement for growth stimulatory molecules and a diminished sensitivity to inhibitory signals.

Question 30

Give a process cancer cells require growth factors for?

Answer 30

Angiogenesis

Question 31

Give two ways in which growth factors may be produced by cancer cells?

Answer 31

cancer cells themselves or by inducement of benign cells around the tumour

Question 32

How is platelet derived growth factor involved in chronic myeloid leukaemia?

Answer 32

• Translocation between chromosomes 5 and 12 leads to formation of fusion gene, with resulting misguided activation of PDGFRB. This is an early event in development of chronic myeloid leukaemia, highlighting the oncogenic potential of PDGF.

Question 33

How has the treatment of lung cancer changed in the last twenty years?

Answer 33

Past
Small cell or non-small cell

Now
Small cell, non-small cell (Squamous cell? If not, adenocarcinoma? If so, EGFR positive or negative?

Question 34

What is a fusion gene?

Answer 34

Forms a receptor which is always on

Question 35

What is the difference in cell staining in polypeptide and steroid receptors?

Answer 35

Polypeptide - Cell surface

Steroid - within cell